The Protective Role of IL-36/IL-36R Signal in Con A-Induced Acute Hepatitis
J Immunol. 2022 Jan 19:ji2100481. doi: 10.4049/jimmunol.2100481. Online ahead of print.ABSTRACTThe IL-36 family, including IL-36α, IL-36β, IL-36γ, and IL-36R antagonist, belong to the IL-1 superfamily. It was reported that IL-36 plays a role in immune diseases. However, it remains unclear how IL-36 regulates inflammation. To determine the role of IL-36/IL-36R signaling pathways, we established an acute hepatitis mouse model (C57BL/6) by i.v. injection of the plant lectin Con A. We found that the levels of IL-36 were increased in the liver after Con A injection. Our results demonstrated the infiltrated neut...
Source: Journal of Immunology - January 20, 2022 Category: Allergy & Immunology Authors: Xiaofang Wang Yuejin Liang Hui Wang Biao Zhang Lynn Soong Jiyang Cai Panpan Yi Xuegong Fan Jiaren Sun Source Type: research

Formation of Calprotectin-Derived Peptides in the Airways of Children with Cystic Fibrosis
J Immunol. 2022 Jan 19:ji2001017. doi: 10.4049/jimmunol.2001017. Online ahead of print.ABSTRACTCalprotectin is released by activated neutrophils along with myeloperoxidase (MPO) and proteases. It plays numerous roles in inflammation and infection, and is used as an inflammatory biomarker. However, calprotectin is readily oxidized by MPO-derived hypohalous acids to form covalent dimers of its S100A8 and S100A9 subunits. The dimers are susceptible to degradation by proteases. We show that detection of human calprotectin by ELISA declines markedly because of its oxidation by hypochlorous acid and subsequent degradation. Also,...
Source: Journal of Immunology - January 20, 2022 Category: Allergy & Immunology Authors: Teagan S Edwards Nina Dickerhof Nicholas J Magon Louise N Paton Peter D Sly Anthony J Kettle Source Type: research

Bidirectional Transport of IgE by CD23 in the Inner Ear of Patients with Meniere's Disease
J Immunol. 2022 Jan 19:ji2100745. doi: 10.4049/jimmunol.2100745. Online ahead of print.ABSTRACTMeniere's disease (MD) is a disorder of the inner ear characterized by episodes of spontaneous vertigo, fluctuating hearing loss, and tinnitus. Recent studies have demonstrated that IgE may play a role in the pathogenesis of MD. Patients with MD (n = 103), acoustic neuroma (n = 5), and healthy subjects (n = 72) were recruited into the study. Serum from the participants was analyzed for IgE and type 2-related cytokines. IgE and CD23 expression levels in vestibular end organs of patients, C57BL/6 mice, or mouse HEI-OC1 cells were a...
Source: Journal of Immunology - January 20, 2022 Category: Allergy & Immunology Authors: Na Zhang Yafeng Lyu Jia Guo Jiahui Liu Yongdong Song Zhaomin Fan Xiaofei Li Na Li Daogong Zhang Haibo Wang Source Type: research

Loss of Ribosomal Protein Paralog Rpl22-like1 Blocks Lymphoid Development without Affecting Protein Synthesis
J Immunol. 2022 Jan 19:ji2100668. doi: 10.4049/jimmunol.2100668. Online ahead of print.ABSTRACTRibosomal proteins are thought to primarily facilitate biogenesis of the ribosome and its ability to synthesize protein. However, in this study, we show that Rpl22-like1 (Rpl22l1) regulates hematopoiesis without affecting ribosome biogenesis or bulk protein synthesis. Conditional loss of murine Rpl22l1 using stage or lineage-restricted Cre drivers impairs development of several hematopoietic lineages. Specifically, Tie2-Cre-mediated ablation of Rpl22l1 in hemogenic endothelium impairs the emergence of embryonic hematopoietic stem...
Source: Journal of Immunology - January 20, 2022 Category: Allergy & Immunology Authors: Shawn P Fahl Robert Sertori Yong Zhang Alejandra V Contreras Bryan Harris Minshi Wang Jacqueline Perrigoue Siddharth Balachandran Brian K Kennedy David L Wiest Source Type: research

Top Reads
J Immunol. 2022 Feb 1;208(3):529-530. doi: 10.4049/jimmunol.2190026.NO ABSTRACTPMID:35042787 | DOI:10.4049/jimmunol.2190026 (Source: Journal of Immunology)
Source: Journal of Immunology - January 19, 2022 Category: Allergy & Immunology Source Type: research

Minimal Information about MHC Multimers (MIAMM)
J Immunol. 2022 Feb 1;208(3):531-537. doi: 10.4049/jimmunol.2100961.ABSTRACTWith the goal of improving the reproducibility and annotatability of MHC multimer reagent data, we present the establishment of a new data standard: Minimal Information about MHC Multimers (https://miamm.lji.org/). Multimers are engineered reagents composed of a ligand and a MHC, which can be represented in a standardized format using ontology terminology. We provide an online Web site to host the details of the standard, as well as a validation tool to assist with the adoption of the standard. We hope that this publication will bring increased awa...
Source: Journal of Immunology - January 19, 2022 Category: Allergy & Immunology Authors: Randi Vita Apurva Mody James A Overton Soren Buus Stephen T Haley Alessandro Sette Vamsee Mallajosyula Mark M Davis Dale L Long Richard A Willis Bjoern Peters John D Altman Source Type: research

Variegated Outcomes of T Cell Activation by Dendritic Cells in the Steady State
J Immunol. 2022 Feb 1;208(3):539-547. doi: 10.4049/jimmunol.2100932.ABSTRACTConventional dendritic cells (cDC) control adaptive immunity by sensing damage- and pathogen-associated molecular patterns and then inducing defined differentiation programs in T cells. Nevertheless, in the absence of specific proimmunogenic innate signals, generally referred to as the steady state, cDC also activate T cells to induce specific functional fates. Consistent with the maintenance of homeostasis, such specific outcomes of T cell activation in the steady state include T cell clonal anergy, deletion, and conversion of peripheral regulator...
Source: Journal of Immunology - January 19, 2022 Category: Allergy & Immunology Authors: Jessica Bourque Daniel Hawiger Source Type: research

Defective STAT5 Activation and Aberrant Expression of BCL6 in Naive CD4 T Cells Enhances Follicular Th Cell-like Differentiation in Patients with Granulomatosis with Polyangiitis
J Immunol. 2022 Jan 17:ji2001331. doi: 10.4049/jimmunol.2001331. Online ahead of print.ABSTRACTGranulomatosis with polyangiitis (GPA) is a potentially fatal small vessel vasculitis of unknown etiology, characterized by anti-neutrophil cytoplasmic autoantibodies, chronic inflammation, and granulomatous tissue damage. T cell dysregulation, comprising decreased regulatory T cell function and increased circulating effector memory follicular Th cells (TFH), is strongly associated with disease pathogenesis, but the mechanisms driving these observations are unknown. We undertook transcriptomic and functional analysis of naive CD4...
Source: Journal of Immunology - January 18, 2022 Category: Allergy & Immunology Authors: Sangmi Kim Lena Boehme Louise Nel Alina Casian Shirish Sangle Estefania Nova-Lamperti Vlad Seitan Jo Spencer Paul Lavender David P D'Cruz Susan John Source Type: research

Innate and Adaptive Immunity to Transfused Allogeneic RBCs in Mice Requires MyD88
J Immunol. 2022 Jan 17:ji2100784. doi: 10.4049/jimmunol.2100784. Online ahead of print.ABSTRACTRBC transfusion therapy is essential for the treatment of anemia. A serious complication of transfusion is the development of non-ABO alloantibodies to polymorphic RBC Ags; yet, mechanisms of alloantibody formation remain unclear. Storage of mouse RBCs before transfusion increases RBC immunogenicity through an unknown mechanism. We previously reported that sterile, stored mouse RBCs activate splenic dendritic cells (DCs), which are required for alloimmunization. Here we transfused mice with allogeneic RBCs to test whether stored ...
Source: Journal of Immunology - January 18, 2022 Category: Allergy & Immunology Authors: Arielle Soldatenko Laura R Hoyt Lan Xu Samuele Calabro Steven M Lewis Antonia E Gallman Krystalyn E Hudson Sean R Stowell Chance J Luckey James C Zimring Dong Liu Manjula Santhanakrishnan Jeanne E Hendrickson Stephanie C Eisenbarth Source Type: research

The < em > Idd2 < /em > Locus Confers Prominent Resistance to Autoimmune Diabetes
J Immunol. 2022 Jan 17:ji2100456. doi: 10.4049/jimmunol.2100456. Online ahead of print.ABSTRACTType 1 diabetes is an autoimmune disease characterized by pancreatic β cell destruction. It is a complex genetic trait driven by>30 genetic loci with parallels between humans and mice. The NOD mouse spontaneously develops autoimmune diabetes and is widely used to identify insulin-dependent diabetes (Idd) genetic loci linked to diabetes susceptibility. Although many Idd loci have been extensively studied, the impact of the Idd2 locus on autoimmune diabetes susceptibility remains to be defined. To address this, we generated...
Source: Journal of Immunology - January 18, 2022 Category: Allergy & Immunology Authors: F élix Lombard-Vadnais Roxanne Collin Jean-Fran çois Daudelin Genevi ève Chabot-Roy Nathalie Labrecque Sylvie Lesage Source Type: research

The Kinetics of COVID-19 Vaccine Response in a Community-Vaccinated Population
J Immunol. 2022 Jan 17:ji2100919. doi: 10.4049/jimmunol.2100919. Online ahead of print.ABSTRACTWe used a noninvasive electrochemical quantitative assay for IgG Abs to SARS-CoV-2 S1 Ag in saliva to investigate the kinetics of Ab response in a community-based population that had received either the Pfizer or Moderna mRNA-based vaccine. Samples were received from a total of 97 individuals, including a subset of 42 individuals who collected samples twice weekly for 3 mo or longer. In all,>840 samples were collected and analyzed. In all individuals, salivary SARS-CoV-2 S1 IgG Ab levels rose sharply in the 2-wk period after t...
Source: Journal of Immunology - January 18, 2022 Category: Allergy & Immunology Authors: Michael K Tu Samantha H Chiang Richard A Bender David T W Wong Charles M Strom Source Type: research

Control of Memory Phenotype T Lymphocyte Homeostasis: Role of Costimulation
J Immunol. 2022 Jan 17:ji2100653. doi: 10.4049/jimmunol.2100653. Online ahead of print.ABSTRACTFoxp3+ T regulatory cells (Tregs), CD4+Foxp3- T cells, and CD8+ T cells are composed of naive phenotype (NP) and memory phenotype (MP) subsets. Ten to 20% of each MP T cell population are cycling (Ki-67+) in vivo. We investigated the contribution of costimulatory (CD28) and coinhibitory (CTLA-4, PD-1) receptors on MP T cell homeostatic proliferation in vivo in the mouse. Blockade of CD28-CD80/CD86 signaling completely abolished MP Tregs and profoundly inhibited MP CD4+Foxp3- T cell proliferation, but it did not affect MP CD8+ T c...
Source: Journal of Immunology - January 18, 2022 Category: Allergy & Immunology Authors: Abir K Panda Yong-Hee Kim Ethan M Shevach Source Type: research

Defective STAT5 Activation and Aberrant Expression of BCL6 in Naive CD4 T Cells Enhances Follicular Th Cell-like Differentiation in Patients with Granulomatosis with Polyangiitis
J Immunol. 2022 Jan 17:ji2001331. doi: 10.4049/jimmunol.2001331. Online ahead of print.ABSTRACTGranulomatosis with polyangiitis (GPA) is a potentially fatal small vessel vasculitis of unknown etiology, characterized by anti-neutrophil cytoplasmic autoantibodies, chronic inflammation, and granulomatous tissue damage. T cell dysregulation, comprising decreased regulatory T cell function and increased circulating effector memory follicular Th cells (TFH), is strongly associated with disease pathogenesis, but the mechanisms driving these observations are unknown. We undertook transcriptomic and functional analysis of naive CD4...
Source: Journal of Immunology - January 18, 2022 Category: Allergy & Immunology Authors: Sangmi Kim Lena Boehme Louise Nel Alina Casian Shirish Sangle Estefania Nova-Lamperti Vlad Seitan Jo Spencer Paul Lavender David P D'Cruz Susan John Source Type: research

Innate and Adaptive Immunity to Transfused Allogeneic RBCs in Mice Requires MyD88
J Immunol. 2022 Jan 17:ji2100784. doi: 10.4049/jimmunol.2100784. Online ahead of print.ABSTRACTRBC transfusion therapy is essential for the treatment of anemia. A serious complication of transfusion is the development of non-ABO alloantibodies to polymorphic RBC Ags; yet, mechanisms of alloantibody formation remain unclear. Storage of mouse RBCs before transfusion increases RBC immunogenicity through an unknown mechanism. We previously reported that sterile, stored mouse RBCs activate splenic dendritic cells (DCs), which are required for alloimmunization. Here we transfused mice with allogeneic RBCs to test whether stored ...
Source: Journal of Immunology - January 18, 2022 Category: Allergy & Immunology Authors: Arielle Soldatenko Laura R Hoyt Lan Xu Samuele Calabro Steven M Lewis Antonia E Gallman Krystalyn E Hudson Sean R Stowell Chance J Luckey James C Zimring Dong Liu Manjula Santhanakrishnan Jeanne E Hendrickson Stephanie C Eisenbarth Source Type: research

The < em > Idd2 < /em > Locus Confers Prominent Resistance to Autoimmune Diabetes
J Immunol. 2022 Jan 17:ji2100456. doi: 10.4049/jimmunol.2100456. Online ahead of print.ABSTRACTType 1 diabetes is an autoimmune disease characterized by pancreatic β cell destruction. It is a complex genetic trait driven by>30 genetic loci with parallels between humans and mice. The NOD mouse spontaneously develops autoimmune diabetes and is widely used to identify insulin-dependent diabetes (Idd) genetic loci linked to diabetes susceptibility. Although many Idd loci have been extensively studied, the impact of the Idd2 locus on autoimmune diabetes susceptibility remains to be defined. To address this, we generated...
Source: Journal of Immunology - January 18, 2022 Category: Allergy & Immunology Authors: F élix Lombard-Vadnais Roxanne Collin Jean-Fran çois Daudelin Genevi ève Chabot-Roy Nathalie Labrecque Sylvie Lesage Source Type: research

The Kinetics of COVID-19 Vaccine Response in a Community-Vaccinated Population
J Immunol. 2022 Jan 17:ji2100919. doi: 10.4049/jimmunol.2100919. Online ahead of print.ABSTRACTWe used a noninvasive electrochemical quantitative assay for IgG Abs to SARS-CoV-2 S1 Ag in saliva to investigate the kinetics of Ab response in a community-based population that had received either the Pfizer or Moderna mRNA-based vaccine. Samples were received from a total of 97 individuals, including a subset of 42 individuals who collected samples twice weekly for 3 mo or longer. In all,>840 samples were collected and analyzed. In all individuals, salivary SARS-CoV-2 S1 IgG Ab levels rose sharply in the 2-wk period after t...
Source: Journal of Immunology - January 18, 2022 Category: Allergy & Immunology Authors: Michael K Tu Samantha H Chiang Richard A Bender David T W Wong Charles M Strom Source Type: research

Control of Memory Phenotype T Lymphocyte Homeostasis: Role of Costimulation
J Immunol. 2022 Jan 17:ji2100653. doi: 10.4049/jimmunol.2100653. Online ahead of print.ABSTRACTFoxp3+ T regulatory cells (Tregs), CD4+Foxp3- T cells, and CD8+ T cells are composed of naive phenotype (NP) and memory phenotype (MP) subsets. Ten to 20% of each MP T cell population are cycling (Ki-67+) in vivo. We investigated the contribution of costimulatory (CD28) and coinhibitory (CTLA-4, PD-1) receptors on MP T cell homeostatic proliferation in vivo in the mouse. Blockade of CD28-CD80/CD86 signaling completely abolished MP Tregs and profoundly inhibited MP CD4+Foxp3- T cell proliferation, but it did not affect MP CD8+ T c...
Source: Journal of Immunology - January 18, 2022 Category: Allergy & Immunology Authors: Abir K Panda Yong-Hee Kim Ethan M Shevach Source Type: research

Bone Marrow Transplantation Rescues Monocyte Recruitment Defect and Improves Cystic Fibrosis in Mice
In this study, we demonstrate that monocytes from CFTRΔF508 mice (CF mice) show defective adhesion under flow. Transplanting CF mice with wild-type (WT) bone marrow after sublethal irradiation replaced most (60-80%) CF monocytes with WT monocytes, significantly improved survival, and reduced inflammation. WT/CF mixed bone marrow chimeras directly demonstrated defective CF monocyte recruitment to the bronchoalveolar lavage and the intestinal lamina propria in vivo. WT mice reconstituted with CF bone marrow also show lethality, suggesting that the CF defect in monocytes is not only necessary but also sufficient to caus...
Source: Journal of Immunology - January 15, 2022 Category: Allergy & Immunology Authors: Zhichao Fan Elise Pitmon Lai Wen Jacqueline Miller Erik Ehinger Rana Herro Wei Liu Ju Chen Zbigniew Mikulski Douglas J Conrad Alex Marki Marco Orecchioni Puja Kumari Yanfang Peipei Zhu Paola M Marcovecchio Catherine C Hedrick Craig A Hodges Vijay A Rathin Source Type: research

Altered Basal Lipid Metabolism Underlies the Functional Impairment of Naive CD8 < sup > + < /sup > T Cells in Elderly Humans
J Immunol. 2022 Jan 14:ji2100194. doi: 10.4049/jimmunol.2100194. Online ahead of print.ABSTRACTAging is associated with functional deficits in the naive T cell compartment, which compromise the generation of de novo immune responses against previously unencountered Ags. The mechanisms that underlie this phenomenon have nonetheless remained unclear. We found that naive CD8+ T cells in elderly humans were prone to apoptosis and proliferated suboptimally in response to stimulation via the TCR. These abnormalities were associated with dysregulated lipid metabolism under homeostatic conditions and enhanced levels of basal activ...
Source: Journal of Immunology - January 15, 2022 Category: Allergy & Immunology Authors: Francesco Nicoli Mariela P Cabral-Piccin Laura Papagno Eleonora Gallerani Mathieu Fusaro Victor Folcher Marion Dubois Emmanuel Clave H élène Vallet Justin J Frere Emma Gostick Sian Llewellyn-Lacey David A Price Antoine Toubert Lo ïc Dupré Jacques Bodd Source Type: research

Regulation of Cutaneous Immunity In  Vivo by Calcitonin Gene-Related Peptide Signaling through Endothelial Cells
J Immunol. 2022 Jan 14:ji2100139. doi: 10.4049/jimmunol.2100139. Online ahead of print.ABSTRACTCalcitonin gene-related peptide (CGRP) can bias the outcome of Ag presentation to responsive T cells in vitro away from Th1-type immunity and toward the Th2 and Th17 poles through actions on endothelial cells (ECs). To test the in vivo significance of this observation, we engineered a mouse lacking functional CGRP receptors on ECs (EC receptor activity modifying protein 1 [RAMP1] knockout mice). On percutaneous immunization to 1-fluoro-2,4-dinitrobenzene, stimulated CD4+ T cells from draining lymph nodes showed significantly redu...
Source: Journal of Immunology - January 15, 2022 Category: Allergy & Immunology Authors: Wanhong Ding Lori L Stohl Jad Saab Shayan Azizi Xi K Zhou Devina Mehta Richard D Granstein Source Type: research

Systematic Determination of TCR-Antigen and Peptide-MHC Binding Kinetics among Field Variants of a < em > Theileria parva < /em > Polymorphic CTL Epitope
In this study, we characterized the amino acids important for MHC class I binding and TCR recognition in the Tp967-75 epitope using alanine scanning and a series of variant peptide sequences to probe these interactions. In a peptide-MHC class I binding assay, we found that the amino acids at positions 1, 2, and 3 were critical for binding to its restricting MHC class I molecule BoLA-1*023:01. With IFN-γ ELISPOT and peptide-MHC class I Tet staining assays on two parasite-specific bovine CTL lines, we showed that amino acids at positions 5-8 in the epitope were required for TCR recognition. Only two of eight naturally ...
Source: Journal of Immunology - January 15, 2022 Category: Allergy & Immunology Authors: Nicholas Svitek Rosemary Saya Houshuang Zhang Vishvanath Nene Lucilla Steinaa Source Type: research

Bone Marrow Transplantation Rescues Monocyte Recruitment Defect and Improves Cystic Fibrosis in Mice
In this study, we demonstrate that monocytes from CFTRΔF508 mice (CF mice) show defective adhesion under flow. Transplanting CF mice with wild-type (WT) bone marrow after sublethal irradiation replaced most (60-80%) CF monocytes with WT monocytes, significantly improved survival, and reduced inflammation. WT/CF mixed bone marrow chimeras directly demonstrated defective CF monocyte recruitment to the bronchoalveolar lavage and the intestinal lamina propria in vivo. WT mice reconstituted with CF bone marrow also show lethality, suggesting that the CF defect in monocytes is not only necessary but also sufficient to caus...
Source: Journal of Immunology - January 15, 2022 Category: Allergy & Immunology Authors: Zhichao Fan Elise Pitmon Lai Wen Jacqueline Miller Erik Ehinger Rana Herro Wei Liu Ju Chen Zbigniew Mikulski Douglas J Conrad Alex Marki Marco Orecchioni Puja Kumari Yanfang Peipei Zhu Paola M Marcovecchio Catherine C Hedrick Craig A Hodges Vijay A Rathin Source Type: research

Altered Basal Lipid Metabolism Underlies the Functional Impairment of Naive CD8 < sup > + < /sup > T Cells in Elderly Humans
J Immunol. 2022 Jan 14:ji2100194. doi: 10.4049/jimmunol.2100194. Online ahead of print.ABSTRACTAging is associated with functional deficits in the naive T cell compartment, which compromise the generation of de novo immune responses against previously unencountered Ags. The mechanisms that underlie this phenomenon have nonetheless remained unclear. We found that naive CD8+ T cells in elderly humans were prone to apoptosis and proliferated suboptimally in response to stimulation via the TCR. These abnormalities were associated with dysregulated lipid metabolism under homeostatic conditions and enhanced levels of basal activ...
Source: Journal of Immunology - January 15, 2022 Category: Allergy & Immunology Authors: Francesco Nicoli Mariela P Cabral-Piccin Laura Papagno Eleonora Gallerani Mathieu Fusaro Victor Folcher Marion Dubois Emmanuel Clave H élène Vallet Justin J Frere Emma Gostick Sian Llewellyn-Lacey David A Price Antoine Toubert Lo ïc Dupré Jacques Bodd Source Type: research

Regulation of Cutaneous Immunity In  Vivo by Calcitonin Gene-Related Peptide Signaling through Endothelial Cells
J Immunol. 2022 Jan 14:ji2100139. doi: 10.4049/jimmunol.2100139. Online ahead of print.ABSTRACTCalcitonin gene-related peptide (CGRP) can bias the outcome of Ag presentation to responsive T cells in vitro away from Th1-type immunity and toward the Th2 and Th17 poles through actions on endothelial cells (ECs). To test the in vivo significance of this observation, we engineered a mouse lacking functional CGRP receptors on ECs (EC receptor activity modifying protein 1 [RAMP1] knockout mice). On percutaneous immunization to 1-fluoro-2,4-dinitrobenzene, stimulated CD4+ T cells from draining lymph nodes showed significantly redu...
Source: Journal of Immunology - January 15, 2022 Category: Allergy & Immunology Authors: Wanhong Ding Lori L Stohl Jad Saab Shayan Azizi Xi K Zhou Devina Mehta Richard D Granstein Source Type: research

Systematic Determination of TCR-Antigen and Peptide-MHC Binding Kinetics among Field Variants of a < em > Theileria parva < /em > Polymorphic CTL Epitope
In this study, we characterized the amino acids important for MHC class I binding and TCR recognition in the Tp967-75 epitope using alanine scanning and a series of variant peptide sequences to probe these interactions. In a peptide-MHC class I binding assay, we found that the amino acids at positions 1, 2, and 3 were critical for binding to its restricting MHC class I molecule BoLA-1*023:01. With IFN-γ ELISPOT and peptide-MHC class I Tet staining assays on two parasite-specific bovine CTL lines, we showed that amino acids at positions 5-8 in the epitope were required for TCR recognition. Only two of eight naturally ...
Source: Journal of Immunology - January 15, 2022 Category: Allergy & Immunology Authors: Nicholas Svitek Rosemary Saya Houshuang Zhang Vishvanath Nene Lucilla Steinaa Source Type: research

Bone Marrow Transplantation Rescues Monocyte Recruitment Defect and Improves Cystic Fibrosis in Mice
In this study, we demonstrate that monocytes from CFTRΔF508 mice (CF mice) show defective adhesion under flow. Transplanting CF mice with wild-type (WT) bone marrow after sublethal irradiation replaced most (60-80%) CF monocytes with WT monocytes, significantly improved survival, and reduced inflammation. WT/CF mixed bone marrow chimeras directly demonstrated defective CF monocyte recruitment to the bronchoalveolar lavage and the intestinal lamina propria in vivo. WT mice reconstituted with CF bone marrow also show lethality, suggesting that the CF defect in monocytes is not only necessary but also sufficient to caus...
Source: Journal of Immunology - January 15, 2022 Category: Allergy & Immunology Authors: Zhichao Fan Elise Pitmon Lai Wen Jacqueline Miller Erik Ehinger Rana Herro Wei Liu Ju Chen Zbigniew Mikulski Douglas J Conrad Alex Marki Marco Orecchioni Puja Kumari Yanfang Peipei Zhu Paola M Marcovecchio Catherine C Hedrick Craig A Hodges Vijay A Rathin Source Type: research

Altered Basal Lipid Metabolism Underlies the Functional Impairment of Naive CD8 < sup > + < /sup > T Cells in Elderly Humans
J Immunol. 2022 Jan 14:ji2100194. doi: 10.4049/jimmunol.2100194. Online ahead of print.ABSTRACTAging is associated with functional deficits in the naive T cell compartment, which compromise the generation of de novo immune responses against previously unencountered Ags. The mechanisms that underlie this phenomenon have nonetheless remained unclear. We found that naive CD8+ T cells in elderly humans were prone to apoptosis and proliferated suboptimally in response to stimulation via the TCR. These abnormalities were associated with dysregulated lipid metabolism under homeostatic conditions and enhanced levels of basal activ...
Source: Journal of Immunology - January 15, 2022 Category: Allergy & Immunology Authors: Francesco Nicoli Mariela P Cabral-Piccin Laura Papagno Eleonora Gallerani Mathieu Fusaro Victor Folcher Marion Dubois Emmanuel Clave H élène Vallet Justin J Frere Emma Gostick Sian Llewellyn-Lacey David A Price Antoine Toubert Lo ïc Dupré Jacques Bodd Source Type: research

Regulation of Cutaneous Immunity In  Vivo by Calcitonin Gene-Related Peptide Signaling through Endothelial Cells
J Immunol. 2022 Jan 14:ji2100139. doi: 10.4049/jimmunol.2100139. Online ahead of print.ABSTRACTCalcitonin gene-related peptide (CGRP) can bias the outcome of Ag presentation to responsive T cells in vitro away from Th1-type immunity and toward the Th2 and Th17 poles through actions on endothelial cells (ECs). To test the in vivo significance of this observation, we engineered a mouse lacking functional CGRP receptors on ECs (EC receptor activity modifying protein 1 [RAMP1] knockout mice). On percutaneous immunization to 1-fluoro-2,4-dinitrobenzene, stimulated CD4+ T cells from draining lymph nodes showed significantly redu...
Source: Journal of Immunology - January 15, 2022 Category: Allergy & Immunology Authors: Wanhong Ding Lori L Stohl Jad Saab Shayan Azizi Xi K Zhou Devina Mehta Richard D Granstein Source Type: research

Systematic Determination of TCR-Antigen and Peptide-MHC Binding Kinetics among Field Variants of a < em > Theileria parva < /em > Polymorphic CTL Epitope
In this study, we characterized the amino acids important for MHC class I binding and TCR recognition in the Tp967-75 epitope using alanine scanning and a series of variant peptide sequences to probe these interactions. In a peptide-MHC class I binding assay, we found that the amino acids at positions 1, 2, and 3 were critical for binding to its restricting MHC class I molecule BoLA-1*023:01. With IFN-γ ELISPOT and peptide-MHC class I Tet staining assays on two parasite-specific bovine CTL lines, we showed that amino acids at positions 5-8 in the epitope were required for TCR recognition. Only two of eight naturally ...
Source: Journal of Immunology - January 15, 2022 Category: Allergy & Immunology Authors: Nicholas Svitek Rosemary Saya Houshuang Zhang Vishvanath Nene Lucilla Steinaa Source Type: research

Respiratory Syncytial Virus Provides Protection against a Subsequent Influenza A Virus Infection
In this study, we examined how the order in which BALB/c mice were infected with both RSV and IAV impacts disease severity. RSV infection prior to an IAV infection was associated with decreased weight loss and increased survival as compared with IAV infection alone. In contrast, IAV infection prior to an RSV infection was associated with similar morbidity and mortality as compared with an IAV infection alone. Our results suggest that the order in which viral infections are acquired plays a critical role in the outcome of disease severity and the host immune response.PMID:35022269 | DOI:10.4049/jimmunol.2000751 (Source: Journal of Immunology)
Source: Journal of Immunology - January 13, 2022 Category: Allergy & Immunology Authors: Stacey M Hartwig Ann M Miller Steven M Varga Source Type: research

Long Noncoding RNA HOTAIRM1 Promotes Immunosuppression in Sepsis by Inducing T Cell Exhaustion
J Immunol. 2022 Jan 12:ji2100709. doi: 10.4049/jimmunol.2100709. Online ahead of print.ABSTRACTSepsis is an acute life-threatening disorder associated with multiorgan dysfunction that remains the leading cause of death in intensive care units. As sepsis progresses, it causes prolonged immunosuppression, which results in sustained mortality, morbidity, and susceptibility to secondary infections. Using a mouse model of sepsis, we found that the long noncoding RNA HOTAIRM1 (HOXA transcript antisense RNA myeloid-specific 1) was highly expressed in mice during the late phase of sepsis. The upregulation of HOTAIRM1 was induced b...
Source: Journal of Immunology - January 13, 2022 Category: Allergy & Immunology Authors: Wankun Chen Jinlong Liu Feng Ge Zhaoyuan Chen Mengdi Qu Ke Nan Jiahui Gu Yi Jiang Shenjia Gao Yun Liao Chengji Wang Hao Zhang Changhong Miao Source Type: research

A Recombinant Ig Fragment (IgCw- γεκ) Comprising the Cγ < sub > 1 < /sub > -C ε < sub > 2-4 < /sub > and C < sub > κ < /sub > Domains Is an Alternative Reagent to Human IgE
In this study, we report the development of a recombinant Ig fragment, designated IgCw-γεκ, as an alternative reagent to human IgE. IgCw-γεκ (∼130 kDa) comprises two hybrid constant H chain regions (Cγ1-Cε2-4, each ∼53 kDa) and two constant κ L chains (Cκ, each ∼12 kDa) and lacks a V domain. The presence of Cγ1 instead of Cε1 within the H chain increased the production yield and facilitated assembly of the H and L chains. IgCw-γεκ was produced in cultured human embryonic kidney 293F cells, with a yield of ∼27...
Source: Journal of Immunology - January 13, 2022 Category: Allergy & Immunology Authors: Minjae Kim Jeonghyun Lee Juho Choi Youngsil Seo Gyeseo Park Jinah Jeon Yerin Jeon Mi-Gi Lee Myung-Hee Kwon Source Type: research

Fewer LAG-3 < sup > + < /sup > T Cells in Relapsing-Remitting Multiple Sclerosis and Type 1 Diabetes
J Immunol. 2022 Jan 12:ji2100850. doi: 10.4049/jimmunol.2100850. Online ahead of print.ABSTRACTThe coinhibitory receptor lymphocyte activation gene 3 (LAG-3) is an immune checkpoint molecule that negatively regulates T cell activation, proliferation, and homeostasis. Blockade or deletion of LAG-3 in autoimmune-prone backgrounds or induced-disease models has been shown to exacerbate disease. We observed significantly fewer LAG-3+ CD4 and CD8 T cells from subjects with relapsing-remitting multiple sclerosis (RRMS) and type 1 diabetes. Low LAG-3 protein expression was linked to alterations in mRNA expression and not cell surf...
Source: Journal of Immunology - January 13, 2022 Category: Allergy & Immunology Authors: Britta E Jones Megan D Maerz Henry T Bahnson Ashwin Somasundaram Lucas H McCarthy Cate Speake Jane H Buckner Source Type: research

Grass Carp Reovirus Nonstructural Proteins Avoid Host Antiviral Immune Response by Targeting the RLR Signaling Pathway
In this study, we report the negative regulations of NS38 and NS80 on the RIG-I-like receptors (RLRs) antiviral signaling pathway and the production of IFNs and IFN-stimulated genes. First, both in the case of overexpression and GCRV infection, NS38 and NS80 inhibited the IFN promoter activation induced by RIG-I, MDA5, MAVS, TBK1, IRF3, and IRF7 and mRNA abundance of key antiviral genes involved in the RLR-mediated signaling. Second, both in the case of overexpression and GCRV infection, NS38 interacted with piscine TBK1 and IRF3, but not with piscine RIG-I, MDA5, MAVS, and TNF receptor-associated factor (TRAF) 3. Whereas ...
Source: Journal of Immunology - January 13, 2022 Category: Allergy & Immunology Authors: Jie Zhang Xiao Man Wu Qin Fang Yong Hong Bi Pin Nie Ming Xian Chang Source Type: research

Diagnostic Value of Circulating Antigens in the Serum of Piglets with Experimental Acute Toxoplasmosis
In this study, we established a model of acute T. gondii infection in Large White pigs. CAg levels peaked between 3 and 5 d after inoculation, and 28 CAgs were identified using an immunoprecipitation-shotgun approach, among which dolichol-phosphate-mannose synthase family protein (TgDPM), C3HC zinc finger-like protein (TgZFLP3), and ribosomal protein RPL7 (TgRPL7) were selected to further investigate their value in the diagnosis of acute toxoplasmosis. Immunofluorescence assays revealed that TgDPM and TgRPL7 were localized in the membrane surface, while TgZFLP3 was localized in the apical end. Western blotting revealed the...
Source: Journal of Immunology - January 13, 2022 Category: Allergy & Immunology Authors: Qi Liu Man-Yu Zhang Bing Zhao Yun Chen Wei Jiang Xiao-Ling Geng Quan Wang Source Type: research

Hepatitis B and Hepatitis C Virus Infection Promote Liver Fibrogenesis through a TGF- β1-Induced OCT4/Nanog Pathway
In conclusion, HBV and HCV independently and cooperatively promote liver fibrogenesis through a TGF-β1-induced OCT4/Nanog-dependent pathway.PMID:35022275 | DOI:10.4049/jimmunol.2001453 (Source: Journal of Immunology)
Source: Journal of Immunology - January 13, 2022 Category: Allergy & Immunology Authors: Wenting Li Xiaoqiong Duan Chuanlong Zhu Xiao Liu Andre J Jeyarajan Min Xu Zeng Tu Qiuju Sheng Dong Chen Chuanwu Zhu Tuo Shao Zhimeng Cheng Shadi Salloum Esperance A Schaefer Annie J Kruger Jacinta A Holmes Raymond T Chung Wenyu Lin Source Type: research

IL-33 Coordinates Innate Defense to Systemic < em > Candid < /em > < em > a albican < /em > < em > s < /em > Infection by Regulating IL-23 and IL-10 in an Opposite Way
In this study, we systematically analyzed the in vivo functions of endogenous IL-33 using Il33 -/- mice and in vitro immune cell culture. Tubular epithelial cells mainly secreted IL-33 in response to systemic C. albicans infection. Il33 -/- mice showed increased mortality and morbidity, which were due to impaired fungal clearance. IL-33 initiated an innate defense mechanism by costimulating dendritic cells to produce IL-23 after systemic C. albicans infection, which in turn promoted the phagocytosis of neutrophils through secretion of GM-CSF by NK cells. The susceptibility of Il33 -/- mice was also associated with increase...
Source: Journal of Immunology - January 13, 2022 Category: Allergy & Immunology Authors: Nu Z N Nguyen Vuvi G Tran Jiyeon Baek Younghee Kim Eun H Youn Seung W Na Sang J Park Su-Kil Seo Byungsuk Kwon Source Type: research

MicroRNA-139 Expression Is Dispensable for the Generation of Influenza-Specific CD8 < sup > + < /sup > T Cell Responses
J Immunol. 2022 Jan 12:ji2000621. doi: 10.4049/jimmunol.2000621. Online ahead of print.ABSTRACTMicroRNAs (miRNAs/miRs) are small, endogenous noncoding RNAs that are important post-transcriptional regulators with clear roles in the development of the immune system and immune responses. Using miRNA microarray profiling, we characterized the expression profile of naive and in vivo generated murine effector antiviral CD8+ T cells. We observed that out of 362 measurable mature miRNAs, 120 were differentially expressed by at least 2-fold in influenza-specific effector CD8+ CTLs compared with naive CD8+ T cells. One miRNA found t...
Source: Journal of Immunology - January 13, 2022 Category: Allergy & Immunology Authors: Jennifer L Hope Manzhi Zhao Christopher J Stairiker Caoimhe H Kiernan Alison J Carey Yvonne M Mueller Marjan van Meurs Inge Brouwers-Haspels Dennis C Otero Eun-Ah Bae Hannah A Faso Alex Maas Hans de Looper Paolo M Fortina Isidore Rigoutsos Linda M Bradley Source Type: research

Respiratory Syncytial Virus Provides Protection against a Subsequent Influenza A Virus Infection
In this study, we examined how the order in which BALB/c mice were infected with both RSV and IAV impacts disease severity. RSV infection prior to an IAV infection was associated with decreased weight loss and increased survival as compared with IAV infection alone. In contrast, IAV infection prior to an RSV infection was associated with similar morbidity and mortality as compared with an IAV infection alone. Our results suggest that the order in which viral infections are acquired plays a critical role in the outcome of disease severity and the host immune response.PMID:35022269 | DOI:10.4049/jimmunol.2000751 (Source: Journal of Immunology)
Source: Journal of Immunology - January 13, 2022 Category: Allergy & Immunology Authors: Stacey M Hartwig Ann M Miller Steven M Varga Source Type: research

Long Noncoding RNA HOTAIRM1 Promotes Immunosuppression in Sepsis by Inducing T Cell Exhaustion
J Immunol. 2022 Jan 12:ji2100709. doi: 10.4049/jimmunol.2100709. Online ahead of print.ABSTRACTSepsis is an acute life-threatening disorder associated with multiorgan dysfunction that remains the leading cause of death in intensive care units. As sepsis progresses, it causes prolonged immunosuppression, which results in sustained mortality, morbidity, and susceptibility to secondary infections. Using a mouse model of sepsis, we found that the long noncoding RNA HOTAIRM1 (HOXA transcript antisense RNA myeloid-specific 1) was highly expressed in mice during the late phase of sepsis. The upregulation of HOTAIRM1 was induced b...
Source: Journal of Immunology - January 13, 2022 Category: Allergy & Immunology Authors: Wankun Chen Jinlong Liu Feng Ge Zhaoyuan Chen Mengdi Qu Ke Nan Jiahui Gu Yi Jiang Shenjia Gao Yun Liao Chengji Wang Hao Zhang Changhong Miao Source Type: research

A Recombinant Ig Fragment (IgCw- γεκ) Comprising the Cγ < sub > 1 < /sub > -C ε < sub > 2-4 < /sub > and C < sub > κ < /sub > Domains Is an Alternative Reagent to Human IgE
In this study, we report the development of a recombinant Ig fragment, designated IgCw-γεκ, as an alternative reagent to human IgE. IgCw-γεκ (∼130 kDa) comprises two hybrid constant H chain regions (Cγ1-Cε2-4, each ∼53 kDa) and two constant κ L chains (Cκ, each ∼12 kDa) and lacks a V domain. The presence of Cγ1 instead of Cε1 within the H chain increased the production yield and facilitated assembly of the H and L chains. IgCw-γεκ was produced in cultured human embryonic kidney 293F cells, with a yield of ∼27...
Source: Journal of Immunology - January 13, 2022 Category: Allergy & Immunology Authors: Minjae Kim Jeonghyun Lee Juho Choi Youngsil Seo Gyeseo Park Jinah Jeon Yerin Jeon Mi-Gi Lee Myung-Hee Kwon Source Type: research

Fewer LAG-3 < sup > + < /sup > T Cells in Relapsing-Remitting Multiple Sclerosis and Type 1 Diabetes
J Immunol. 2022 Jan 12:ji2100850. doi: 10.4049/jimmunol.2100850. Online ahead of print.ABSTRACTThe coinhibitory receptor lymphocyte activation gene 3 (LAG-3) is an immune checkpoint molecule that negatively regulates T cell activation, proliferation, and homeostasis. Blockade or deletion of LAG-3 in autoimmune-prone backgrounds or induced-disease models has been shown to exacerbate disease. We observed significantly fewer LAG-3+ CD4 and CD8 T cells from subjects with relapsing-remitting multiple sclerosis (RRMS) and type 1 diabetes. Low LAG-3 protein expression was linked to alterations in mRNA expression and not cell surf...
Source: Journal of Immunology - January 13, 2022 Category: Allergy & Immunology Authors: Britta E Jones Megan D Maerz Henry T Bahnson Ashwin Somasundaram Lucas H McCarthy Cate Speake Jane H Buckner Source Type: research

Grass Carp Reovirus Nonstructural Proteins Avoid Host Antiviral Immune Response by Targeting the RLR Signaling Pathway
In this study, we report the negative regulations of NS38 and NS80 on the RIG-I-like receptors (RLRs) antiviral signaling pathway and the production of IFNs and IFN-stimulated genes. First, both in the case of overexpression and GCRV infection, NS38 and NS80 inhibited the IFN promoter activation induced by RIG-I, MDA5, MAVS, TBK1, IRF3, and IRF7 and mRNA abundance of key antiviral genes involved in the RLR-mediated signaling. Second, both in the case of overexpression and GCRV infection, NS38 interacted with piscine TBK1 and IRF3, but not with piscine RIG-I, MDA5, MAVS, and TNF receptor-associated factor (TRAF) 3. Whereas ...
Source: Journal of Immunology - January 13, 2022 Category: Allergy & Immunology Authors: Jie Zhang Xiao Man Wu Qin Fang Yong Hong Bi Pin Nie Ming Xian Chang Source Type: research

Diagnostic Value of Circulating Antigens in the Serum of Piglets with Experimental Acute Toxoplasmosis
In this study, we established a model of acute T. gondii infection in Large White pigs. CAg levels peaked between 3 and 5 d after inoculation, and 28 CAgs were identified using an immunoprecipitation-shotgun approach, among which dolichol-phosphate-mannose synthase family protein (TgDPM), C3HC zinc finger-like protein (TgZFLP3), and ribosomal protein RPL7 (TgRPL7) were selected to further investigate their value in the diagnosis of acute toxoplasmosis. Immunofluorescence assays revealed that TgDPM and TgRPL7 were localized in the membrane surface, while TgZFLP3 was localized in the apical end. Western blotting revealed the...
Source: Journal of Immunology - January 13, 2022 Category: Allergy & Immunology Authors: Qi Liu Man-Yu Zhang Bing Zhao Yun Chen Wei Jiang Xiao-Ling Geng Quan Wang Source Type: research

Hepatitis B and Hepatitis C Virus Infection Promote Liver Fibrogenesis through a TGF- β1-Induced OCT4/Nanog Pathway
In conclusion, HBV and HCV independently and cooperatively promote liver fibrogenesis through a TGF-β1-induced OCT4/Nanog-dependent pathway.PMID:35022275 | DOI:10.4049/jimmunol.2001453 (Source: Journal of Immunology)
Source: Journal of Immunology - January 13, 2022 Category: Allergy & Immunology Authors: Wenting Li Xiaoqiong Duan Chuanlong Zhu Xiao Liu Andre J Jeyarajan Min Xu Zeng Tu Qiuju Sheng Dong Chen Chuanwu Zhu Tuo Shao Zhimeng Cheng Shadi Salloum Esperance A Schaefer Annie J Kruger Jacinta A Holmes Raymond T Chung Wenyu Lin Source Type: research

IL-33 Coordinates Innate Defense to Systemic < em > Candid < /em > < em > a albican < /em > < em > s < /em > Infection by Regulating IL-23 and IL-10 in an Opposite Way
In this study, we systematically analyzed the in vivo functions of endogenous IL-33 using Il33 -/- mice and in vitro immune cell culture. Tubular epithelial cells mainly secreted IL-33 in response to systemic C. albicans infection. Il33 -/- mice showed increased mortality and morbidity, which were due to impaired fungal clearance. IL-33 initiated an innate defense mechanism by costimulating dendritic cells to produce IL-23 after systemic C. albicans infection, which in turn promoted the phagocytosis of neutrophils through secretion of GM-CSF by NK cells. The susceptibility of Il33 -/- mice was also associated with increase...
Source: Journal of Immunology - January 13, 2022 Category: Allergy & Immunology Authors: Nu Z N Nguyen Vuvi G Tran Jiyeon Baek Younghee Kim Eun H Youn Seung W Na Sang J Park Su-Kil Seo Byungsuk Kwon Source Type: research

MicroRNA-139 Expression Is Dispensable for the Generation of Influenza-Specific CD8 < sup > + < /sup > T Cell Responses
J Immunol. 2022 Jan 12:ji2000621. doi: 10.4049/jimmunol.2000621. Online ahead of print.ABSTRACTMicroRNAs (miRNAs/miRs) are small, endogenous noncoding RNAs that are important post-transcriptional regulators with clear roles in the development of the immune system and immune responses. Using miRNA microarray profiling, we characterized the expression profile of naive and in vivo generated murine effector antiviral CD8+ T cells. We observed that out of 362 measurable mature miRNAs, 120 were differentially expressed by at least 2-fold in influenza-specific effector CD8+ CTLs compared with naive CD8+ T cells. One miRNA found t...
Source: Journal of Immunology - January 13, 2022 Category: Allergy & Immunology Authors: Jennifer L Hope Manzhi Zhao Christopher J Stairiker Caoimhe H Kiernan Alison J Carey Yvonne M Mueller Marjan van Meurs Inge Brouwers-Haspels Dennis C Otero Eun-Ah Bae Hannah A Faso Alex Maas Hans de Looper Paolo M Fortina Isidore Rigoutsos Linda M Bradley Source Type: research

Respiratory Syncytial Virus Provides Protection against a Subsequent Influenza A Virus Infection
In this study, we examined how the order in which BALB/c mice were infected with both RSV and IAV impacts disease severity. RSV infection prior to an IAV infection was associated with decreased weight loss and increased survival as compared with IAV infection alone. In contrast, IAV infection prior to an RSV infection was associated with similar morbidity and mortality as compared with an IAV infection alone. Our results suggest that the order in which viral infections are acquired plays a critical role in the outcome of disease severity and the host immune response.PMID:35022269 | DOI:10.4049/jimmunol.2000751 (Source: Journal of Immunology)
Source: Journal of Immunology - January 13, 2022 Category: Allergy & Immunology Authors: Stacey M Hartwig Ann M Miller Steven M Varga Source Type: research

Long Noncoding RNA HOTAIRM1 Promotes Immunosuppression in Sepsis by Inducing T Cell Exhaustion
J Immunol. 2022 Jan 12:ji2100709. doi: 10.4049/jimmunol.2100709. Online ahead of print.ABSTRACTSepsis is an acute life-threatening disorder associated with multiorgan dysfunction that remains the leading cause of death in intensive care units. As sepsis progresses, it causes prolonged immunosuppression, which results in sustained mortality, morbidity, and susceptibility to secondary infections. Using a mouse model of sepsis, we found that the long noncoding RNA HOTAIRM1 (HOXA transcript antisense RNA myeloid-specific 1) was highly expressed in mice during the late phase of sepsis. The upregulation of HOTAIRM1 was induced b...
Source: Journal of Immunology - January 13, 2022 Category: Allergy & Immunology Authors: Wankun Chen Jinlong Liu Feng Ge Zhaoyuan Chen Mengdi Qu Ke Nan Jiahui Gu Yi Jiang Shenjia Gao Yun Liao Chengji Wang Hao Zhang Changhong Miao Source Type: research

A Recombinant Ig Fragment (IgCw- γεκ) Comprising the Cγ < sub > 1 < /sub > -C ε < sub > 2-4 < /sub > and C < sub > κ < /sub > Domains Is an Alternative Reagent to Human IgE
In this study, we report the development of a recombinant Ig fragment, designated IgCw-γεκ, as an alternative reagent to human IgE. IgCw-γεκ (∼130 kDa) comprises two hybrid constant H chain regions (Cγ1-Cε2-4, each ∼53 kDa) and two constant κ L chains (Cκ, each ∼12 kDa) and lacks a V domain. The presence of Cγ1 instead of Cε1 within the H chain increased the production yield and facilitated assembly of the H and L chains. IgCw-γεκ was produced in cultured human embryonic kidney 293F cells, with a yield of ∼27...
Source: Journal of Immunology - January 13, 2022 Category: Allergy & Immunology Authors: Minjae Kim Jeonghyun Lee Juho Choi Youngsil Seo Gyeseo Park Jinah Jeon Yerin Jeon Mi-Gi Lee Myung-Hee Kwon Source Type: research