IL-6 Signaling Protects Zebrafish Larvae during < em > Staphylococcus epidermidis < /em > Infection in a Bath Immersion Model
J Immunol. 2021 Sep 20:ji2000714. doi: 10.4049/jimmunol.2000714. Online ahead of print.ABSTRACTThe host immune responses to Staphylococcus epidermidis, a frequent cause of nosocomial infections, are not well understood. We have established a bath immersion model of this infection in zebrafish (Danio rerio) larvae. Macrophages play a primary role in the host immune response and are involved in clearance of infection in the larvae. S. epidermidis infection results in upregulation of tlr-2 There is marked inflammation characterized by heightened NF-κB signaling and elevation of several proinflammatory cytokines. There i...
Source: Journal of Immunology - September 21, 2021 Category: Allergy & Immunology Authors: P Thamarasseri Dhanagovind Prabeer K Kujur Rajeeb K Swain Sanjita Banerjee Source Type: research

Elevated N-Linked Glycosylation of IgG V Regions in Myasthenia Gravis Disease Subtypes
J Immunol. 2021 Sep 20:ji2100225. doi: 10.4049/jimmunol.2100225. Online ahead of print.ABSTRACTElevated N-linked glycosylation of IgG V regions (IgG-VN-Glyc) is an emerging molecular phenotype associated with autoimmune disorders. To test the broader specificity of elevated IgG-VN-Glyc, we studied patients with distinct subtypes of myasthenia gravis (MG), a B cell-mediated autoimmune disease. Our experimental design focused on examining the B cell repertoire and total IgG. It specifically included adaptive immune receptor repertoire sequencing to quantify and characterize N-linked glycosylation sites in the circulating BCR...
Source: Journal of Immunology - September 21, 2021 Category: Allergy & Immunology Authors: Caleigh Mandel-Brehm Miriam L Fichtner Ruoyi Jiang Valerie J Winton Sara E Vazquez Minh C Pham Kenneth B Hoehn Neil L Kelleher Richard J Nowak Steven H Kleinstein Michael R Wilson Joseph L DeRisi Kevin C O'Connor Source Type: research

Cutting Edge: Intestinal IL-17A Receptor Signaling Specifically Regulates High-Fat Diet-Mediated, Microbiota-Driven Metabolic Disorders
J Immunol. 2021 Sep 20:ji2000986. doi: 10.4049/jimmunol.2000986. Online ahead of print.ABSTRACTPrevious studies indicate that IL-17A plays an important role in mediating the intestinal microbiota and systemic metabolic functions. However, it is not known where IL-17RA signaling occurs to mediate these effects. To investigate this question, we used intestinal epithelial-specific (Il17raIEC ) and liver-specific (Il17raLiver ) IL-17RA knockout mice as well as littermate control mice. Our results indicate that intestinal IL-17RA signaling helps mediate systemic metabolic functions upon exposure to prolonged high-fat diet. Il17...
Source: Journal of Immunology - September 21, 2021 Category: Allergy & Immunology Authors: Stephen J Gaudino Huakang Huang Makheni Jean-Pierre Preet Joshi Michael Beaupre Cody Kempen Hoi Tong Wong Pawan Kumar Source Type: research

Modern World Influences on the Microbiome and Their Consequences for Immune-Mediated Disease
J Immunol. 2021 Oct 1;207(7):1695-1696. doi: 10.4049/jimmunol.2190016.NO ABSTRACTPMID:34544809 | DOI:10.4049/jimmunol.2190016 (Source: Journal of Immunology)
Source: Journal of Immunology - September 21, 2021 Category: Allergy & Immunology Authors: Cathryn R Nagler Source Type: research

Top Reads
J Immunol. 2021 Oct 1;207(7):1697. doi: 10.4049/jimmunol.2190017.NO ABSTRACTPMID:34544810 | DOI:10.4049/jimmunol.2190017 (Source: Journal of Immunology)
Source: Journal of Immunology - September 21, 2021 Category: Allergy & Immunology Source Type: research

Inhaled Adjuvants and Eosinophilic Airway Inflammation in Asthma: Is a Little Bit of Lipopolysaccharide the Key to Allergen Sensitization?
J Immunol. 2021 Oct 1;207(7):1699-1701. doi: 10.4049/jimmunol.2100542.NO ABSTRACTPMID:34544811 | DOI:10.4049/jimmunol.2100542 (Source: Journal of Immunology)
Source: Journal of Immunology - September 21, 2021 Category: Allergy & Immunology Authors: Steve N Georas Source Type: research

Natural versus Laboratory World: Incorporating Wild-Derived Microbiota into Preclinical Rodent Models
J Immunol. 2021 Oct 1;207(7):1703-1709. doi: 10.4049/jimmunol.2100426.ABSTRACTAdvances in data collection (high-throughput shotgun metagenomics, transcriptomics, and metabolomics) and analysis (bioinformatics and multiomics) led to the realization that all mammals are metaorganisms, shaped not only by their own genome but also by the genomes of the microbes that colonize them. To date, most studies have focused on the bacterial microbiome, whereas curated databases for viruses, fungi, and protozoa are still evolving. Studies on the interdependency of microbial kingdoms and their combined effects on host physiology are just...
Source: Journal of Immunology - September 21, 2021 Category: Allergy & Immunology Authors: Ji Hoon Oh Barbara Rehermann Source Type: research

A Modern-World View of Host-Microbiota-Pathogen Interactions
J Immunol. 2021 Oct 1;207(7):1710-1718. doi: 10.4049/jimmunol.2100215.ABSTRACTThe microbiota-the diverse set of commensal microbes that normally colonize humans-represents the first line of defense against infectious diseases. In this review, we summarize the direct and indirect mechanisms by which the microbiota modulates susceptibility to, and severity of, infections, with a focus on immunological mechanisms. Moreover, we highlight some of the ways that modern-world lifestyles have influenced the structure-function relationship between the microbiota and infectious diseases. Ultimately, understanding how the microbiota i...
Source: Journal of Immunology - September 21, 2021 Category: Allergy & Immunology Authors: Chin Yee Tan Zeni E Ramirez Neeraj K Surana Source Type: research

Microbiota-Immune Interactions Regulate Metabolic Disease
J Immunol. 2021 Oct 1;207(7):1719-1724. doi: 10.4049/jimmunol.2100419.ABSTRACTMetabolic diseases are common worldwide and include diseases of overnutrition, such as obesity, or undernutrition, such as kwashiorkor. Both the immune system and the microbiota contribute to a variety of metabolic diseases; however, these two processes have largely been studied independently of one another in this context. The gastrointestinal system houses the greatest density of microbes but also houses one of the largest collections of immune molecules, especially Abs. The IgA isotype dominates the Ab landscape at mucosal sites, and a number ...
Source: Journal of Immunology - September 21, 2021 Category: Allergy & Immunology Authors: Kendra A Klag June L Round Source Type: research

Small Molecule Metabolites at the Host-Microbiota Interface
J Immunol. 2021 Oct 1;207(7):1725-1733. doi: 10.4049/jimmunol.2100528.ABSTRACTThe trillions of bacteria that constitutively colonize the human gut collectively generate thousands of unique small molecules. These microbial metabolites can accumulate both locally and systemically and potentially influence nearly all aspects of mammalian biology, including immunity, metabolism, and even mood and behavior. In this review, we briefly summarize recent work identifying bioactive microbiota metabolites, the means through which they are synthesized, and their effects on host physiology. Rather than offering an exhaustive list of al...
Source: Journal of Immunology - September 21, 2021 Category: Allergy & Immunology Authors: Jason D Bishai Noah W Palm Source Type: research

IL-6 Signaling Protects Zebrafish Larvae during < em > Staphylococcus epidermidis < /em > Infection in a Bath Immersion Model
J Immunol. 2021 Sep 20:ji2000714. doi: 10.4049/jimmunol.2000714. Online ahead of print.ABSTRACTThe host immune responses to Staphylococcus epidermidis, a frequent cause of nosocomial infections, are not well understood. We have established a bath immersion model of this infection in zebrafish (Danio rerio) larvae. Macrophages play a primary role in the host immune response and are involved in clearance of infection in the larvae. S. epidermidis infection results in upregulation of tlr-2 There is marked inflammation characterized by heightened NF-κB signaling and elevation of several proinflammatory cytokines. There i...
Source: Journal of Immunology - September 21, 2021 Category: Allergy & Immunology Authors: P Thamarasseri Dhanagovind Prabeer K Kujur Rajeeb K Swain Sanjita Banerjee Source Type: research

Elevated N-Linked Glycosylation of IgG V Regions in Myasthenia Gravis Disease Subtypes
J Immunol. 2021 Sep 20:ji2100225. doi: 10.4049/jimmunol.2100225. Online ahead of print.ABSTRACTElevated N-linked glycosylation of IgG V regions (IgG-VN-Glyc) is an emerging molecular phenotype associated with autoimmune disorders. To test the broader specificity of elevated IgG-VN-Glyc, we studied patients with distinct subtypes of myasthenia gravis (MG), a B cell-mediated autoimmune disease. Our experimental design focused on examining the B cell repertoire and total IgG. It specifically included adaptive immune receptor repertoire sequencing to quantify and characterize N-linked glycosylation sites in the circulating BCR...
Source: Journal of Immunology - September 21, 2021 Category: Allergy & Immunology Authors: Caleigh Mandel-Brehm Miriam L Fichtner Ruoyi Jiang Valerie J Winton Sara E Vazquez Minh C Pham Kenneth B Hoehn Neil L Kelleher Richard J Nowak Steven H Kleinstein Michael R Wilson Joseph L DeRisi Kevin C O'Connor Source Type: research

Cutting Edge: Intestinal IL-17A Receptor Signaling Specifically Regulates High-Fat Diet-Mediated, Microbiota-Driven Metabolic Disorders
J Immunol. 2021 Sep 20:ji2000986. doi: 10.4049/jimmunol.2000986. Online ahead of print.ABSTRACTPrevious studies indicate that IL-17A plays an important role in mediating the intestinal microbiota and systemic metabolic functions. However, it is not known where IL-17RA signaling occurs to mediate these effects. To investigate this question, we used intestinal epithelial-specific (Il17raIEC ) and liver-specific (Il17raLiver ) IL-17RA knockout mice as well as littermate control mice. Our results indicate that intestinal IL-17RA signaling helps mediate systemic metabolic functions upon exposure to prolonged high-fat diet. Il17...
Source: Journal of Immunology - September 21, 2021 Category: Allergy & Immunology Authors: Stephen J Gaudino Huakang Huang Makheni Jean-Pierre Preet Joshi Michael Beaupre Cody Kempen Hoi Tong Wong Pawan Kumar Source Type: research

Modern World Influences on the Microbiome and Their Consequences for Immune-Mediated Disease
J Immunol. 2021 Oct 1;207(7):1695-1696. doi: 10.4049/jimmunol.2190016.NO ABSTRACTPMID:34544809 | DOI:10.4049/jimmunol.2190016 (Source: Journal of Immunology)
Source: Journal of Immunology - September 21, 2021 Category: Allergy & Immunology Authors: Cathryn R Nagler Source Type: research

Top Reads
J Immunol. 2021 Oct 1;207(7):1697. doi: 10.4049/jimmunol.2190017.NO ABSTRACTPMID:34544810 | DOI:10.4049/jimmunol.2190017 (Source: Journal of Immunology)
Source: Journal of Immunology - September 21, 2021 Category: Allergy & Immunology Source Type: research

Inhaled Adjuvants and Eosinophilic Airway Inflammation in Asthma: Is a Little Bit of Lipopolysaccharide the Key to Allergen Sensitization?
J Immunol. 2021 Oct 1;207(7):1699-1701. doi: 10.4049/jimmunol.2100542.NO ABSTRACTPMID:34544811 | DOI:10.4049/jimmunol.2100542 (Source: Journal of Immunology)
Source: Journal of Immunology - September 21, 2021 Category: Allergy & Immunology Authors: Steve N Georas Source Type: research

Natural versus Laboratory World: Incorporating Wild-Derived Microbiota into Preclinical Rodent Models
J Immunol. 2021 Oct 1;207(7):1703-1709. doi: 10.4049/jimmunol.2100426.ABSTRACTAdvances in data collection (high-throughput shotgun metagenomics, transcriptomics, and metabolomics) and analysis (bioinformatics and multiomics) led to the realization that all mammals are metaorganisms, shaped not only by their own genome but also by the genomes of the microbes that colonize them. To date, most studies have focused on the bacterial microbiome, whereas curated databases for viruses, fungi, and protozoa are still evolving. Studies on the interdependency of microbial kingdoms and their combined effects on host physiology are just...
Source: Journal of Immunology - September 21, 2021 Category: Allergy & Immunology Authors: Ji Hoon Oh Barbara Rehermann Source Type: research

A Modern-World View of Host-Microbiota-Pathogen Interactions
J Immunol. 2021 Oct 1;207(7):1710-1718. doi: 10.4049/jimmunol.2100215.ABSTRACTThe microbiota-the diverse set of commensal microbes that normally colonize humans-represents the first line of defense against infectious diseases. In this review, we summarize the direct and indirect mechanisms by which the microbiota modulates susceptibility to, and severity of, infections, with a focus on immunological mechanisms. Moreover, we highlight some of the ways that modern-world lifestyles have influenced the structure-function relationship between the microbiota and infectious diseases. Ultimately, understanding how the microbiota i...
Source: Journal of Immunology - September 21, 2021 Category: Allergy & Immunology Authors: Chin Yee Tan Zeni E Ramirez Neeraj K Surana Source Type: research

Microbiota-Immune Interactions Regulate Metabolic Disease
J Immunol. 2021 Oct 1;207(7):1719-1724. doi: 10.4049/jimmunol.2100419.ABSTRACTMetabolic diseases are common worldwide and include diseases of overnutrition, such as obesity, or undernutrition, such as kwashiorkor. Both the immune system and the microbiota contribute to a variety of metabolic diseases; however, these two processes have largely been studied independently of one another in this context. The gastrointestinal system houses the greatest density of microbes but also houses one of the largest collections of immune molecules, especially Abs. The IgA isotype dominates the Ab landscape at mucosal sites, and a number ...
Source: Journal of Immunology - September 21, 2021 Category: Allergy & Immunology Authors: Kendra A Klag June L Round Source Type: research

Small Molecule Metabolites at the Host-Microbiota Interface
J Immunol. 2021 Oct 1;207(7):1725-1733. doi: 10.4049/jimmunol.2100528.ABSTRACTThe trillions of bacteria that constitutively colonize the human gut collectively generate thousands of unique small molecules. These microbial metabolites can accumulate both locally and systemically and potentially influence nearly all aspects of mammalian biology, including immunity, metabolism, and even mood and behavior. In this review, we briefly summarize recent work identifying bioactive microbiota metabolites, the means through which they are synthesized, and their effects on host physiology. Rather than offering an exhaustive list of al...
Source: Journal of Immunology - September 21, 2021 Category: Allergy & Immunology Authors: Jason D Bishai Noah W Palm Source Type: research

The Development and Survival of Thymic Epithelial Cells Require TSC1-Dependent Negative Regulation of mTORC1 Activity
J Immunol. 2021 Sep 17:ji2100463. doi: 10.4049/jimmunol.2100463. Online ahead of print.ABSTRACTThymic epithelial cells (TECs) are critical for the development and generation of functionally competent T cells. Until now, the mechanism that regulates the survival of TECs is poorly understood. In the current study, we found that Tsc1 controls the homeostasis of medullary TECs (mTECs) by inhibiting lysosomal-mediated apoptosis pathway in mice. TEC-specific deletion of Tsc1 predominately decreased the cell number of mTECs and, to a lesser content, affected the development cortical TECs. The defect of mTECs caused by Tsc1 defici...
Source: Journal of Immunology - September 18, 2021 Category: Allergy & Immunology Authors: Zhanfeng Liang Qian Zhang Zhaoqi Zhang Lina Sun Xue Dong Tianxiu Li Liang Tan Xubiao Xie Liguang Sun Yong Zhao Source Type: research

Peptide Presentations of Marsupial MHC Class I Visualize Immune Features of Lower Mammals Paralleled with Bats
This study identified a series of possum MHC I Trvu-UB*01:01 binding peptides derived from wobbly possum disease virus (WPDV), a lethal virus of both captive and feral possum populations, and unveiled the structure of marsupial peptide/MHC I complex. Notably, we found the two brushtail possum-specific insertions, the 3-aa Ile52Glu53Arg54 and 1-aa Arg154 insertions are located in the Trvu-UB*01:01 peptide binding groove (PBG). The 3-aa insertion plays a pivotal role in maintaining the stability of the N terminus of Trvu-UB*01:01 PBG. This aspect of marsupial PBG is unexpectedly similar to the bat MHC I Ptal-N*01:01 and is s...
Source: Journal of Immunology - September 18, 2021 Category: Allergy & Immunology Authors: Pengyan Wang Can Yue Kefang Liu Dan Lu Sai Liu Sijia Yao Xin Li Xiaoling Su Keyi Ren Yan Chai Jianxun Qi Yingze Zhao Yongliang Lou Zeyu Sun George F Gao William J Liu Source Type: research

The PD-1 Regulatory Axis Inhibits T Cell-Independent B Cell Memory Generation and Reactivation
J Immunol. 2021 Sep 17:ji2100336. doi: 10.4049/jimmunol.2100336. Online ahead of print.ABSTRACTThe inability of T cell-independent type 2 (TI-2) Ags to induce recall responses is a poorly understood facet of humoral immunity, yet critically important for improving vaccines. Using normal and VHB1-8 transgenic mice, we demonstrate that B cell-intrinsic PD-1 expression negatively regulates TI-2 memory B cell (Bmem) generation and reactivation in part through interacting with PDL1 and PDL2 on non-Ag-specific cells. We also identified a significant role for PDL2 expression on Bmems in inhibiting reactivation and Ab production, ...
Source: Journal of Immunology - September 18, 2021 Category: Allergy & Immunology Authors: M Ariel Spurrier Jamie E Jennings-Gee Christina A Daly Karen M Haas Source Type: research

Macrophage-Derived Osteopontin Influences the Amplification of < em > Cryptococcus neoformans < /em > -Promoting Type 2 Immune Response
J Immunol. 2021 Sep 15:ji2100202. doi: 10.4049/jimmunol.2100202. Online ahead of print.ABSTRACTA multifunctional glycoprotein, osteopontin (OPN), can modulate the function of macrophages, resulting in either protective or deleterious effects in various inflammatory diseases and infection in the lungs. Although macrophages play the critical roles in mediating host defenses against cryptococcosis or cryptococcal pathogenesis, the involvement of macrophage-derived OPN in pulmonary infection caused by fungus Cryptococcus has not been elucidated. Thus, our current study aimed to investigate the contribution of OPN to the regula...
Source: Journal of Immunology - September 16, 2021 Category: Allergy & Immunology Authors: Adithap Hansakon Chin Wen Png Yongliang Zhang Pornpimon Angkasekwinai Source Type: research

Enhancing Antigen Presentation and Inducing Antigen-Specific Immune Tolerance with Amphiphilic Peptides
In this study, we show that a lipophilic modification at the N-terminal end of CD4+ epitopes (lipo-peptides) dramatically improves peptide Ag presentation. We designed amphiphilic lipo-peptides to efficiently target APCs in the lymph nodes by binding and trafficking with endogenous albumin. Additionally, we show that lipophilic modification anchors the peptide into the membranes of APCs, enabling a bivalent cell-surface Ag presentation. The s.c. injected lipo-peptide accumulates in the APCs in the lymph node, enhances the potency and duration of peptide Ag presentation by APCs, and induces Ag-specific immune tolerance that...
Source: Journal of Immunology - September 16, 2021 Category: Allergy & Immunology Authors: Meng Li Arata Itoh Jingchao Xi Chunsong Yu Yuehong Wu William M Ridgway Haipeng Liu Source Type: research

Decidual Inflammation Drives Chemokine-Mediated Immune Infiltration Contributing to Term Labor
J Immunol. 2021 Sep 15:ji2100493. doi: 10.4049/jimmunol.2100493. Online ahead of print.ABSTRACTInfiltration of maternal peripheral leukocytes into the uterine tissues is a critical event occurring before, during, and after term labor (TL). In this article, we investigate the contribution of uterine smooth muscle (myometrium) and pregnant endometrium (decidua) to the inflammatory process during human TL. We hypothesize that labor-related physiological inflammation is orchestrated by uterine-secreted cytokines, which dually activate the uterine vascular endothelium and maternal leukocytes to promote their adhesion and infilt...
Source: Journal of Immunology - September 16, 2021 Category: Allergy & Immunology Authors: Oksana Shynlova Adam Boros-Rausch Tali Farine Kristina M Adams Waldorf Caroline Dunk Stephen J Lye Source Type: research

Leaked Mitochondrial C1QBP Inhibits Activation of the DNA Sensor cGAS
In this study, we analyzed cGAS protein interactome in mouse RAW264.7 macrophages and found that cGAS interacted with C1QBP. C1QBP predominantly localized in the mitochondria and leaked into the cytosol during DNA virus infection. The leaked C1QBP bound the NTase domain of cGAS and inhibited cGAS enzymatic activity in cells and in vitro. Overexpression of the cytosolic form of C1QBP inhibited cytosolic DNA-elicited innate immune responses and promoted HSV-1 infection. By contrast, deficiency of C1QBP led to the elevated innate immune responses and impaired HSV-1 infection. Taken together, our study suggests that C1QBP is a...
Source: Journal of Immunology - September 16, 2021 Category: Allergy & Immunology Authors: Kun Song Yakun Wu Bishi Fu Lingyan Wang Wenzhuo Hao Fang Hua Yiwen Sun Martin E Dorf Shitao Li Source Type: research

ROR γt Promotes Foxp3 Expression by Antagonizing the Effector Program in Colonic Regulatory T Cells
J Immunol. 2021 Sep 13:ji2100175. doi: 10.4049/jimmunol.2100175. Online ahead of print.ABSTRACTRORγt is the master transcription factor for the Th17 cells. Paradoxically, in the intestine, RORγt is coexpressed in peripherally induced regulatory T cells (pTregs) together with Foxp3, the master transcription factor for Tregs. Unexpectedly, by an unknown mechanism, colonic RORγt+ Tregs show an enhanced suppressor function and prevent intestinal inflammation more efficiently than RORγt-nonexpressing pTregs. Although studies have elucidated the function of RORγt in Th17 cells, how RORγt regul...
Source: Journal of Immunology - September 14, 2021 Category: Allergy & Immunology Authors: Suniti Bhaumik Michel Edwar Mickael Monica Moran Marion Spell Rajatava Basu Source Type: research

ROR γt Promotes Foxp3 Expression by Antagonizing the Effector Program in Colonic Regulatory T Cells
J Immunol. 2021 Sep 13:ji2100175. doi: 10.4049/jimmunol.2100175. Online ahead of print.ABSTRACTRORγt is the master transcription factor for the Th17 cells. Paradoxically, in the intestine, RORγt is coexpressed in peripherally induced regulatory T cells (pTregs) together with Foxp3, the master transcription factor for Tregs. Unexpectedly, by an unknown mechanism, colonic RORγt+ Tregs show an enhanced suppressor function and prevent intestinal inflammation more efficiently than RORγt-nonexpressing pTregs. Although studies have elucidated the function of RORγt in Th17 cells, how RORγt regul...
Source: Journal of Immunology - September 14, 2021 Category: Allergy & Immunology Authors: Suniti Bhaumik Michel Edwar Mickael Monica Moran Marion Spell Rajatava Basu Source Type: research

ROR γt Promotes Foxp3 Expression by Antagonizing the Effector Program in Colonic Regulatory T Cells
J Immunol. 2021 Sep 13:ji2100175. doi: 10.4049/jimmunol.2100175. Online ahead of print.ABSTRACTRORγt is the master transcription factor for the Th17 cells. Paradoxically, in the intestine, RORγt is coexpressed in peripherally induced regulatory T cells (pTregs) together with Foxp3, the master transcription factor for Tregs. Unexpectedly, by an unknown mechanism, colonic RORγt+ Tregs show an enhanced suppressor function and prevent intestinal inflammation more efficiently than RORγt-nonexpressing pTregs. Although studies have elucidated the function of RORγt in Th17 cells, how RORγt regul...
Source: Journal of Immunology - September 14, 2021 Category: Allergy & Immunology Authors: Suniti Bhaumik Michel Edwar Mickael Monica Moran Marion Spell Rajatava Basu Source Type: research

ROR γt Promotes Foxp3 Expression by Antagonizing the Effector Program in Colonic Regulatory T Cells
J Immunol. 2021 Sep 13:ji2100175. doi: 10.4049/jimmunol.2100175. Online ahead of print.ABSTRACTRORγt is the master transcription factor for the Th17 cells. Paradoxically, in the intestine, RORγt is coexpressed in peripherally induced regulatory T cells (pTregs) together with Foxp3, the master transcription factor for Tregs. Unexpectedly, by an unknown mechanism, colonic RORγt+ Tregs show an enhanced suppressor function and prevent intestinal inflammation more efficiently than RORγt-nonexpressing pTregs. Although studies have elucidated the function of RORγt in Th17 cells, how RORγt regul...
Source: Journal of Immunology - September 14, 2021 Category: Allergy & Immunology Authors: Suniti Bhaumik Michel Edwar Mickael Monica Moran Marion Spell Rajatava Basu Source Type: research

ROR γt Promotes Foxp3 Expression by Antagonizing the Effector Program in Colonic Regulatory T Cells
J Immunol. 2021 Sep 13:ji2100175. doi: 10.4049/jimmunol.2100175. Online ahead of print.ABSTRACTRORγt is the master transcription factor for the Th17 cells. Paradoxically, in the intestine, RORγt is coexpressed in peripherally induced regulatory T cells (pTregs) together with Foxp3, the master transcription factor for Tregs. Unexpectedly, by an unknown mechanism, colonic RORγt+ Tregs show an enhanced suppressor function and prevent intestinal inflammation more efficiently than RORγt-nonexpressing pTregs. Although studies have elucidated the function of RORγt in Th17 cells, how RORγt regul...
Source: Journal of Immunology - September 14, 2021 Category: Allergy & Immunology Authors: Suniti Bhaumik Michel Edwar Mickael Monica Moran Marion Spell Rajatava Basu Source Type: research

ROR γt Promotes Foxp3 Expression by Antagonizing the Effector Program in Colonic Regulatory T Cells
J Immunol. 2021 Sep 13:ji2100175. doi: 10.4049/jimmunol.2100175. Online ahead of print.ABSTRACTRORγt is the master transcription factor for the Th17 cells. Paradoxically, in the intestine, RORγt is coexpressed in peripherally induced regulatory T cells (pTregs) together with Foxp3, the master transcription factor for Tregs. Unexpectedly, by an unknown mechanism, colonic RORγt+ Tregs show an enhanced suppressor function and prevent intestinal inflammation more efficiently than RORγt-nonexpressing pTregs. Although studies have elucidated the function of RORγt in Th17 cells, how RORγt regul...
Source: Journal of Immunology - September 14, 2021 Category: Allergy & Immunology Authors: Suniti Bhaumik Michel Edwar Mickael Monica Moran Marion Spell Rajatava Basu Source Type: research

Macrophagic Extracellular Vesicle CXCL2 Recruits and Activates the Neutrophil CXCR2/PKC/NOX4 Axis in Sepsis
This study provides information regarding the mechanisms underlying neutrophil recruitment to tissues and proposes innovative strategies and targets for the treatment of sepsis.PMID:34507947 | DOI:10.4049/jimmunol.2100229 (Source: Journal of Immunology)
Source: Journal of Immunology - September 11, 2021 Category: Allergy & Immunology Authors: Guozhen Wang Weichang Huang Shuanghu Wang Jun Wang Wanfu Cui Wenyong Zhang Anni Lou Shiyu Geng Xu Li Source Type: research

Microglial NLRP3 Inflammasome Activation upon TLR2 and TLR5 Ligation by Distinct α-Synuclein Assemblies
J Immunol. 2021 Sep 10:ji2100035. doi: 10.4049/jimmunol.2100035. Online ahead of print.ABSTRACTParkinson's disease (PD) is the second most common age-related neurodegenerative disorder and is characterized by the formation of cellular inclusions inside neurons that are rich in an abnormal form of the protein α-synuclein (α-syn). Microglia are the CNS resident immune cells that react to misfolded proteins through pattern recognition receptor ligation and activation of signaling transduction pathways. Here, we studied activation of primary microglia isolated from wild-type mouse by distinct α-syn forms and ...
Source: Journal of Immunology - September 11, 2021 Category: Allergy & Immunology Authors: Hannah Scheiblich Luc Bousset Stephanie Schwartz Angelika Griep Eicke Latz Ronald Melki Michael T Heneka Source Type: research

Self-Renewing Islet TCF1 < sup > + < /sup > CD8 T Cells Undergo IL-27-Controlled Differentiation to Become TCF1 < sup > - < /sup > Terminal Effectors during the Progression of Type 1 Diabetes
J Immunol. 2021 Sep 10:ji2100362. doi: 10.4049/jimmunol.2100362. Online ahead of print.ABSTRACTIn type 1 diabetes (T1D) autoreactive CD8 T cells infiltrate pancreatic islets and destroy insulin-producing β cells. Progression to T1D onset is a chronic process, which suggests that the effector activity of β-cell autoreactive CD8 T cells needs to be maintained throughout the course of disease development. The mechanism that sustains diabetogenic CD8 T cell effectors during the course of T1D progression has not been completely defined. Here we used single-cell RNA sequencing to gain further insight into the phenotypi...
Source: Journal of Immunology - September 11, 2021 Category: Allergy & Immunology Authors: Ashley E Ciecko David M Schauder Bardees Foda Galina Petrova Moujtaba Y Kasmani Robert Burns Chien-Wei Lin William R Drobyski Weiguo Cui Yi-Guang Chen Source Type: research

CD4 T Cell Responses to < em > Theileria parva < /em > in Immune Cattle Recognize a Diverse Set of Parasite Antigens Presented on the Surface of Infected Lymphoblasts
J Immunol. 2021 Sep 10:ji2100331. doi: 10.4049/jimmunol.2100331. Online ahead of print.ABSTRACTParasite-specific CD8 T cell responses play a key role in mediating immunity against Theileria parva in cattle (Bos taurus), and there is evidence that efficient induction of these responses requires CD4 T cell responses. However, information on the antigenic specificity of the CD4 T cell response is lacking. The current study used a high-throughput system for Ag identification using CD4 T cells from immune animals to screen a library of ∼40,000 synthetic peptides representing 499 T. parva gene products. Use of CD4 T cells fr...
Source: Journal of Immunology - September 11, 2021 Category: Allergy & Immunology Authors: W Ivan Morrison Adriana Aguado Tara A Sheldrake Nicholas C Palmateer Olukemi O Ifeonu Kyle Tretina Keith Parsons Emilio Fenoy Timothy Connelley Morten Nielsen Joana C Silva Source Type: research

Macrophagic Extracellular Vesicle CXCL2 Recruits and Activates the Neutrophil CXCR2/PKC/NOX4 Axis in Sepsis
This study provides information regarding the mechanisms underlying neutrophil recruitment to tissues and proposes innovative strategies and targets for the treatment of sepsis.PMID:34507947 | DOI:10.4049/jimmunol.2100229 (Source: Journal of Immunology)
Source: Journal of Immunology - September 11, 2021 Category: Allergy & Immunology Authors: Guozhen Wang Weichang Huang Shuanghu Wang Jun Wang Wanfu Cui Wenyong Zhang Anni Lou Shiyu Geng Xu Li Source Type: research

Microglial NLRP3 Inflammasome Activation upon TLR2 and TLR5 Ligation by Distinct α-Synuclein Assemblies
J Immunol. 2021 Sep 10:ji2100035. doi: 10.4049/jimmunol.2100035. Online ahead of print.ABSTRACTParkinson's disease (PD) is the second most common age-related neurodegenerative disorder and is characterized by the formation of cellular inclusions inside neurons that are rich in an abnormal form of the protein α-synuclein (α-syn). Microglia are the CNS resident immune cells that react to misfolded proteins through pattern recognition receptor ligation and activation of signaling transduction pathways. Here, we studied activation of primary microglia isolated from wild-type mouse by distinct α-syn forms and ...
Source: Journal of Immunology - September 11, 2021 Category: Allergy & Immunology Authors: Hannah Scheiblich Luc Bousset Stephanie Schwartz Angelika Griep Eicke Latz Ronald Melki Michael T Heneka Source Type: research

Self-Renewing Islet TCF1 < sup > + < /sup > CD8 T Cells Undergo IL-27-Controlled Differentiation to Become TCF1 < sup > - < /sup > Terminal Effectors during the Progression of Type 1 Diabetes
J Immunol. 2021 Sep 10:ji2100362. doi: 10.4049/jimmunol.2100362. Online ahead of print.ABSTRACTIn type 1 diabetes (T1D) autoreactive CD8 T cells infiltrate pancreatic islets and destroy insulin-producing β cells. Progression to T1D onset is a chronic process, which suggests that the effector activity of β-cell autoreactive CD8 T cells needs to be maintained throughout the course of disease development. The mechanism that sustains diabetogenic CD8 T cell effectors during the course of T1D progression has not been completely defined. Here we used single-cell RNA sequencing to gain further insight into the phenotypi...
Source: Journal of Immunology - September 11, 2021 Category: Allergy & Immunology Authors: Ashley E Ciecko David M Schauder Bardees Foda Galina Petrova Moujtaba Y Kasmani Robert Burns Chien-Wei Lin William R Drobyski Weiguo Cui Yi-Guang Chen Source Type: research

CD4 T Cell Responses to < em > Theileria parva < /em > in Immune Cattle Recognize a Diverse Set of Parasite Antigens Presented on the Surface of Infected Lymphoblasts
J Immunol. 2021 Sep 10:ji2100331. doi: 10.4049/jimmunol.2100331. Online ahead of print.ABSTRACTParasite-specific CD8 T cell responses play a key role in mediating immunity against Theileria parva in cattle (Bos taurus), and there is evidence that efficient induction of these responses requires CD4 T cell responses. However, information on the antigenic specificity of the CD4 T cell response is lacking. The current study used a high-throughput system for Ag identification using CD4 T cells from immune animals to screen a library of ∼40,000 synthetic peptides representing 499 T. parva gene products. Use of CD4 T cells fr...
Source: Journal of Immunology - September 11, 2021 Category: Allergy & Immunology Authors: W Ivan Morrison Adriana Aguado Tara A Sheldrake Nicholas C Palmateer Olukemi O Ifeonu Kyle Tretina Keith Parsons Emilio Fenoy Timothy Connelley Morten Nielsen Joana C Silva Source Type: research

Macrophagic Extracellular Vesicle CXCL2 Recruits and Activates the Neutrophil CXCR2/PKC/NOX4 Axis in Sepsis
This study provides information regarding the mechanisms underlying neutrophil recruitment to tissues and proposes innovative strategies and targets for the treatment of sepsis.PMID:34507947 | DOI:10.4049/jimmunol.2100229 (Source: Journal of Immunology)
Source: Journal of Immunology - September 11, 2021 Category: Allergy & Immunology Authors: Guozhen Wang Weichang Huang Shuanghu Wang Jun Wang Wanfu Cui Wenyong Zhang Anni Lou Shiyu Geng Xu Li Source Type: research

Microglial NLRP3 Inflammasome Activation upon TLR2 and TLR5 Ligation by Distinct α-Synuclein Assemblies
J Immunol. 2021 Sep 10:ji2100035. doi: 10.4049/jimmunol.2100035. Online ahead of print.ABSTRACTParkinson's disease (PD) is the second most common age-related neurodegenerative disorder and is characterized by the formation of cellular inclusions inside neurons that are rich in an abnormal form of the protein α-synuclein (α-syn). Microglia are the CNS resident immune cells that react to misfolded proteins through pattern recognition receptor ligation and activation of signaling transduction pathways. Here, we studied activation of primary microglia isolated from wild-type mouse by distinct α-syn forms and ...
Source: Journal of Immunology - September 11, 2021 Category: Allergy & Immunology Authors: Hannah Scheiblich Luc Bousset Stephanie Schwartz Angelika Griep Eicke Latz Ronald Melki Michael T Heneka Source Type: research

Self-Renewing Islet TCF1 < sup > + < /sup > CD8 T Cells Undergo IL-27-Controlled Differentiation to Become TCF1 < sup > - < /sup > Terminal Effectors during the Progression of Type 1 Diabetes
J Immunol. 2021 Sep 10:ji2100362. doi: 10.4049/jimmunol.2100362. Online ahead of print.ABSTRACTIn type 1 diabetes (T1D) autoreactive CD8 T cells infiltrate pancreatic islets and destroy insulin-producing β cells. Progression to T1D onset is a chronic process, which suggests that the effector activity of β-cell autoreactive CD8 T cells needs to be maintained throughout the course of disease development. The mechanism that sustains diabetogenic CD8 T cell effectors during the course of T1D progression has not been completely defined. Here we used single-cell RNA sequencing to gain further insight into the phenotypi...
Source: Journal of Immunology - September 11, 2021 Category: Allergy & Immunology Authors: Ashley E Ciecko David M Schauder Bardees Foda Galina Petrova Moujtaba Y Kasmani Robert Burns Chien-Wei Lin William R Drobyski Weiguo Cui Yi-Guang Chen Source Type: research

CD4 T Cell Responses to < em > Theileria parva < /em > in Immune Cattle Recognize a Diverse Set of Parasite Antigens Presented on the Surface of Infected Lymphoblasts
J Immunol. 2021 Sep 10:ji2100331. doi: 10.4049/jimmunol.2100331. Online ahead of print.ABSTRACTParasite-specific CD8 T cell responses play a key role in mediating immunity against Theileria parva in cattle (Bos taurus), and there is evidence that efficient induction of these responses requires CD4 T cell responses. However, information on the antigenic specificity of the CD4 T cell response is lacking. The current study used a high-throughput system for Ag identification using CD4 T cells from immune animals to screen a library of ∼40,000 synthetic peptides representing 499 T. parva gene products. Use of CD4 T cells fr...
Source: Journal of Immunology - September 11, 2021 Category: Allergy & Immunology Authors: W Ivan Morrison Adriana Aguado Tara A Sheldrake Nicholas C Palmateer Olukemi O Ifeonu Kyle Tretina Keith Parsons Emilio Fenoy Timothy Connelley Morten Nielsen Joana C Silva Source Type: research

KAP1-Mediated Epigenetic Suppression in Anti-RNA Viral Responses by Direct Targeting RIG-I and MDA5
In this study, we show that KAP1 attenuates RNA viral infection-induced type I IFNs and facilitates viral replication by inhibiting RIG-I/MDA5 expression in primary peritoneal macrophages (PMs) of C57BL/6J mice. Kap1 deficiency increases IFN-β expression and inhibits vesicular stomatitis virus replication in C57BL/6J mice in vivo. Mechanistically, KAP1 binds to the promoter regions of Ddx58 and Ifih1 and promotes the establishment of repressive histone marks in primary PMs of C57BL/6J mice. Concordantly, KAP1 suppresses the expression of RIG-I and MDA5 at the transcriptional level in primary PMs of C57BL/6J mice. Our ...
Source: Journal of Immunology - September 9, 2021 Category: Allergy & Immunology Authors: Qi Li Ying Qin Wenwen Wang Mutian Jia Wei Zhao Chunyuan Zhao Source Type: research

< em > Lactobacillus rhamnosus < /em > GG Promotes Early B Lineage Development and IgA Production in the Lamina Propria in Piglets
In conclusion, LGG could promote early B cell differentiation and development in the intestinal LP in piglets and might contribute to promoting IgA production via secretion of p40, which interacts with the membrane receptors on IPEC-J2 and induces them to secrete APRIL. Our study will provide insight to aid in better utilization of probiotics to increase human health.PMID:34497150 | DOI:10.4049/jimmunol.2100102 (Source: Journal of Immunology)
Source: Journal of Immunology - September 9, 2021 Category: Allergy & Immunology Authors: Yu-Bei Jin Xin Cao Chun-Wei Shi Bo Feng Hai-Bin Huang Yan-Long Jiang Jian-Zhong Wang Gui-Lian Yang Wen-Tao Yang Chun-Feng Wang Source Type: research

Phosphoinositide 3-Kinase δ Inhibition Improves Neutrophil Bacterial Killing in Critically Ill Patients at High Risk of Infection
J Immunol. 2021 Sep 8:ji2000603. doi: 10.4049/jimmunol.2000603. Online ahead of print.ABSTRACTAcquired neutrophil dysfunction frequently develops during critical illness, independently increasing the risk for intensive care unit-acquired infection. PI3Kδ is implicated in driving neutrophil dysfunction and can potentially be targeted pharmacologically. The aims of this study were to determine whether PI3Kδ inhibition reverses dysfunction in neutrophils from critically ill patients and to describe potential mechanisms. Neutrophils were isolated from blood taken from critically ill patients requiring intubation an...
Source: Journal of Immunology - September 9, 2021 Category: Allergy & Immunology Authors: Jonathan Scott Marie-H élène Ruchaud-Sparagano Kathryn Musgrave Alistair I Roy Stephen E Wright John D Perry Andrew Conway Morris Anthony J Rostron A John Simpson Source Type: research

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J Immunol. 2021 Sep 15;207(6):1495. doi: 10.4049/jimmunol.2190015.NO ABSTRACTPMID:34493603 | DOI:10.4049/jimmunol.2190015 (Source: Journal of Immunology)
Source: Journal of Immunology - September 8, 2021 Category: Allergy & Immunology Source Type: research

An Updated Model for the Epigenetic Regulation of Effector and Memory CD8 < sup > + < /sup > T Cell Differentiation
J Immunol. 2021 Sep 15;207(6):1497-1505. doi: 10.4049/jimmunol.2100633.ABSTRACTNaive CD8+ T cells, upon encountering their cognate Ag in vivo, clonally expand and differentiate into distinct cell fates, regulated by transcription factors and epigenetic modulators. Several models have been proposed to explain the differentiation of CTLs, although none fully recapitulate the experimental evidence. In this review article, we will summarize the latest research on the epigenetic regulation of CTL differentiation as well as provide a combined model that contemplates them.PMID:34493604 | DOI:10.4049/jimmunol.2100633 (Source: Journal of Immunology)
Source: Journal of Immunology - September 8, 2021 Category: Allergy & Immunology Authors: Tianhao Xu Renata M Pereira Gustavo J Martinez Source Type: research