Murine MHC-Deficient Nonobese Diabetic Mice Carrying Human HLA-DQ8 Develop Severe Myocarditis and Myositis in Response to Anti-PD-1 Immune Checkpoint Inhibitor Cancer Therapy
This study sheds light on underlying immunological mechanisms in ICI myocarditis and provides the basis for further detailed analyses of diagnostic and therapeutic strategies.PMID:38426910 | DOI:10.4049/jimmunol.2300841 (Source: Journal of Immunology)
Source: Journal of Immunology - March 1, 2024 Category: Allergy & Immunology Authors: Jeremy J Racine John F Bachman Ji-Gang Zhang Adel Misherghi Raheem Khadour Sana Kaisar Olivia Bedard Catherine Jenkins Annie Abbott Elvira Forte Peter Rainer Nadia Rosenthal Susanne Sattler David V Serreze Source Type: research

Repositioning the Early Pathology of Type 1 Diabetes to the Extraislet Vasculature
J Immunol. 2024 Mar 1:ji2300769. doi: 10.4049/jimmunol.2300769. Online ahead of print.ABSTRACTType 1 diabetes (T1D) is a prototypic T cell-mediated autoimmune disease. Because the islets of Langerhans are insulated from blood vessels by a double basement membrane and lack detectable lymphatic drainage, interactions between endocrine and circulating T cells are not permitted. Thus, we hypothesized that initiation and progression of anti-islet immunity required islet neolymphangiogenesis to allow T cell access to the islet. Combining microscopy and single cell approaches, the timing of this phenomenon in mice was situated be...
Source: Journal of Immunology - March 1, 2024 Category: Allergy & Immunology Authors: Anne Costanzo Don Clarke Marie Holt Siddhartha Sharma Kenna Nagy Xuqian Tan Lisa Kain Brian Abe Sandrine Luce Christian Boitard Tine Wyseure Laurent O Mosnier Andrew I Su Catherine Grimes M G Finn Paul B Savage Michael Gottschalk Jeremy Pettus Luc Teyton Source Type: research

YTHDC1/CRM1 Facilitates m6A-Modified circRNA388 Nuclear Export to Induce Coelomocyte Autophagy via the miR-2008/ULK Axis in Apostichopus japonicus
In this study, we identified m6A-modified circRNA388 from cultured sea cucumber (Apostichopus japonicus) coelomocytes, which was mainly detected in cytoplasm after Vibrio splendidus infection. A knockdown assay indicated that cytoplasm circRNA388 promoted coelomocyte autophagy and decreased the number of intracellular V. splendidus. Mechanistically, the circRNA388 in the cytoplasm directly sponged miR-2008 to block its interaction with Unc-51-like kinase 1 from A. japonicus (AjULK) and further promoted autophagy to resist V. splendidus infection. More importantly, we found that m6A modification was vital to circRNA388 nucl...
Source: Journal of Immunology - March 1, 2024 Category: Allergy & Immunology Authors: Jiqing Liu Yina Shao Chenghua Li Source Type: research

Murine MHC-Deficient Nonobese Diabetic Mice Carrying Human HLA-DQ8 Develop Severe Myocarditis and Myositis in Response to Anti-PD-1 Immune Checkpoint Inhibitor Cancer Therapy
This study sheds light on underlying immunological mechanisms in ICI myocarditis and provides the basis for further detailed analyses of diagnostic and therapeutic strategies.PMID:38426910 | DOI:10.4049/jimmunol.2300841 (Source: Journal of Immunology)
Source: Journal of Immunology - March 1, 2024 Category: Allergy & Immunology Authors: Jeremy J Racine John F Bachman Ji-Gang Zhang Adel Misherghi Raheem Khadour Sana Kaisar Olivia Bedard Catherine Jenkins Annie Abbott Elvira Forte Peter Rainer Nadia Rosenthal Susanne Sattler David V Serreze Source Type: research

Retraction: Ku86 Variant Expression and Function in Multiple Myeloma Cells Is Associated with Increased Sensitivity to DNA Damage
J Immunol. 2024 Feb 28:ji2400070. doi: 10.4049/jimmunol.2400070. Online ahead of print.ABSTRACTWe wish to retract the article titled "Ku86 Variant Expression and Function in Multiple Myeloma Cells Is Associated with Increased Sensitivity to DNA Damage" by Yu-Tzu Tai, Gerrard Teoh, Boris Lin, Faith E. Davies, Dharminder Chauhan, Steven P. Treon, Noopur Raje, Teru Hideshima, Yoshihito Shima, Klaus Podar, and Kenneth C. Anderson, The Journal of Immunology, 2000, 165:6347-6355. There are concerns about the reliability of certain data, arising from errors in the assembly of Figs. 1B, 1D. The authors have concluded that these fi...
Source: Journal of Immunology - February 28, 2024 Category: Allergy & Immunology Authors: Yu-Tzu Tai Gerrard Teoh Boris Lin Faith E Davies Dharminder Chauhan Steven P Treon Noopur Raje Teru Hideshima Yoshihito Shima Klaus Podar Kenneth C Anderson Source Type: research

Granzyme F: Exhaustion Marker and Modulator of Chimeric Antigen Receptor T Cell-Mediated Cytotoxicity
In this study, we show that mouse CD8+ tumor-infiltrating lymphocytes (TILs) express a unique array of granzymes relative to CD8 T cells outside the tumor microenvironment in multiple tumor models. Granzyme F was one of the most highly upregulated genes in TILs and was exclusively detected in PD1/TIM3 double-positive CD8 TILs. To determine the function of granzyme F and to improve the cytotoxic response to leukemia, we constructed chimeric Ag receptor T cells to overexpress a single granzyme, granzyme F or the better-characterized granzyme A or B. Using these doubly recombinant T cells, we demonstrated that granzyme F expr...
Source: Journal of Immunology - February 28, 2024 Category: Allergy & Immunology Authors: Zachary L Z Hay Dale D Kim Jennifer M Cimons Jennifer R Knapp M Eric Kohler Mary Quansah Tiffany M Z úñiga Faye A Camp Mayumi Fujita Xiao-Jing Wang Brian P O'Connor Jill E Slansky Source Type: research

Plitidepsin as an Immunomodulator against Respiratory Viral Infections
J Immunol. 2024 Feb 28:ji2300426. doi: 10.4049/jimmunol.2300426. Online ahead of print.ABSTRACTPlitidepsin is a host-targeted compound known for inducing a strong anti-SARS-CoV-2 activity, as well as for having the capacity of reducing lung inflammation. Because IL-6 is one of the main cytokines involved in acute respiratory distress syndrome, the effect of plitidepsin in IL-6 secretion in different in vitro and in vivo experimental models was studied. A strong plitidepsin-mediated reduction of IL-6 was found in human monocyte-derived macrophages exposed to nonproductive SARS-CoV-2. In resiquimod (a ligand of TLR7/8)-stimu...
Source: Journal of Immunology - February 28, 2024 Category: Allergy & Immunology Authors: Alejandro Losada Nuria Izquierdo-Useros Pablo Aviles J úlia Vergara-Alert Irene Latino Joaquim Segal és Santiago F Gonzalez Carmen Cuevas D àlia Raïch-Regué Mar ía J Muñoz-Alonso Daniel Perez-Zsolt Jordana Mu ñoz-Basagoiti Jordi Rodon Lauren A Cha Source Type: research

Single-Cell Analysis Reveals a Subset of High IL-12p40-Secreting Dendritic Cells within Mouse Bone Marrow-Derived Macrophages Differentiated with M-CSF
In this study, we report that M-CSF-differentiated murine bone marrow-derived macrophages (BMDMs) exhibit extreme heterogeneity in the production of IL-12, a key proinflammatory cytokine linking innate and adaptive immunity. A microwell secretion assay revealed that a small fraction of BMDMs stimulated with LPS secrete most IL-12p40, and we confirmed that this is due to extremely high expression of Il12b, the gene encoding IL-12p40, in a subset of cells. Using an Il12b-YFP reporter mouse, we isolated cells with high LPS-induced Il12b expression and found that this subset was enriched for genes associated with the DC lineag...
Source: Journal of Immunology - February 28, 2024 Category: Allergy & Immunology Authors: Kate Bridges Gabriela A Pizzurro Mihir Khunte Meibin Chen Erick Salvador Rocha Amanda F Alexander Victor Bass Laura N Kellman Janani Baskaran Kathryn Miller-Jensen Source Type: research

Retraction: Ku86 Variant Expression and Function in Multiple Myeloma Cells Is Associated with Increased Sensitivity to DNA Damage
J Immunol. 2024 Feb 28:ji2400070. doi: 10.4049/jimmunol.2400070. Online ahead of print.ABSTRACTWe wish to retract the article titled "Ku86 Variant Expression and Function in Multiple Myeloma Cells Is Associated with Increased Sensitivity to DNA Damage" by Yu-Tzu Tai, Gerrard Teoh, Boris Lin, Faith E. Davies, Dharminder Chauhan, Steven P. Treon, Noopur Raje, Teru Hideshima, Yoshihito Shima, Klaus Podar, and Kenneth C. Anderson, The Journal of Immunology, 2000, 165:6347-6355. There are concerns about the reliability of certain data, arising from errors in the assembly of Figs. 1B, 1D. The authors have concluded that these fi...
Source: Journal of Immunology - February 28, 2024 Category: Allergy & Immunology Authors: Yu-Tzu Tai Gerrard Teoh Boris Lin Faith E Davies Dharminder Chauhan Steven P Treon Noopur Raje Teru Hideshima Yoshihito Shima Klaus Podar Kenneth C Anderson Source Type: research

Granzyme F: Exhaustion Marker and Modulator of Chimeric Antigen Receptor T Cell-Mediated Cytotoxicity
In this study, we show that mouse CD8+ tumor-infiltrating lymphocytes (TILs) express a unique array of granzymes relative to CD8 T cells outside the tumor microenvironment in multiple tumor models. Granzyme F was one of the most highly upregulated genes in TILs and was exclusively detected in PD1/TIM3 double-positive CD8 TILs. To determine the function of granzyme F and to improve the cytotoxic response to leukemia, we constructed chimeric Ag receptor T cells to overexpress a single granzyme, granzyme F or the better-characterized granzyme A or B. Using these doubly recombinant T cells, we demonstrated that granzyme F expr...
Source: Journal of Immunology - February 28, 2024 Category: Allergy & Immunology Authors: Zachary L Z Hay Dale D Kim Jennifer M Cimons Jennifer R Knapp M Eric Kohler Mary Quansah Tiffany M Z úñiga Faye A Camp Mayumi Fujita Xiao-Jing Wang Brian P O'Connor Jill E Slansky Source Type: research

Plitidepsin as an Immunomodulator against Respiratory Viral Infections
J Immunol. 2024 Feb 28:ji2300426. doi: 10.4049/jimmunol.2300426. Online ahead of print.ABSTRACTPlitidepsin is a host-targeted compound known for inducing a strong anti-SARS-CoV-2 activity, as well as for having the capacity of reducing lung inflammation. Because IL-6 is one of the main cytokines involved in acute respiratory distress syndrome, the effect of plitidepsin in IL-6 secretion in different in vitro and in vivo experimental models was studied. A strong plitidepsin-mediated reduction of IL-6 was found in human monocyte-derived macrophages exposed to nonproductive SARS-CoV-2. In resiquimod (a ligand of TLR7/8)-stimu...
Source: Journal of Immunology - February 28, 2024 Category: Allergy & Immunology Authors: Alejandro Losada Nuria Izquierdo-Useros Pablo Aviles J úlia Vergara-Alert Irene Latino Joaquim Segal és Santiago F Gonzalez Carmen Cuevas D àlia Raïch-Regué Mar ía J Muñoz-Alonso Daniel Perez-Zsolt Jordana Mu ñoz-Basagoiti Jordi Rodon Lauren A Cha Source Type: research

Single-Cell Analysis Reveals a Subset of High IL-12p40-Secreting Dendritic Cells within Mouse Bone Marrow-Derived Macrophages Differentiated with M-CSF
In this study, we report that M-CSF-differentiated murine bone marrow-derived macrophages (BMDMs) exhibit extreme heterogeneity in the production of IL-12, a key proinflammatory cytokine linking innate and adaptive immunity. A microwell secretion assay revealed that a small fraction of BMDMs stimulated with LPS secrete most IL-12p40, and we confirmed that this is due to extremely high expression of Il12b, the gene encoding IL-12p40, in a subset of cells. Using an Il12b-YFP reporter mouse, we isolated cells with high LPS-induced Il12b expression and found that this subset was enriched for genes associated with the DC lineag...
Source: Journal of Immunology - February 28, 2024 Category: Allergy & Immunology Authors: Kate Bridges Gabriela A Pizzurro Mihir Khunte Meibin Chen Erick Salvador Rocha Amanda F Alexander Victor Bass Laura N Kellman Janani Baskaran Kathryn Miller-Jensen Source Type: research

Correction: Myeloid Heterogeneity Mediates Acute Exacerbations of Pulmonary Fibrosis
J Immunol. 2024 Feb 26:ji2400069. doi: 10.4049/jimmunol.2400069. Online ahead of print.ABSTRACTWe thank Denise Stanford and the UAB Cystic Fibrosis Research Center Assay Core (The University of Alabama at Birmingham, Birmingham, AL) for assistance with microCT acquisition and image processing. Additional support was provided by the UAB Research and Development Program from the Cystic Fibrosis Foundation (Grant ROWE19RO [DAVIS]).PMID:38407351 | DOI:10.4049/jimmunol.2400069 (Source: Journal of Immunology)
Source: Journal of Immunology - February 26, 2024 Category: Allergy & Immunology Authors: Jennifer L Larson-Casey Komal Saleem Ranu Surolia Jyotsana Pandey Matthias Mack Veena B Antony Sandeep Bodduluri Surya P Bhatt Steven R Duncan A Brent Carter Source Type: research

Induction of MTHFD2 in Macrophages Inhibits Reactive Oxygen Species-mediated NF- κB Activation and Protects against Inflammatory Responses
In this study, we show that MTHFD2 was upregulated by LPS in murine macrophages upon activation of the TLR4-MyD88-IKKα/β-NF-κB signaling pathway. MTHFD2 significantly attenuated LPS-induced macrophage proinflammatory cytokine production through its enzymatic activity. Notably, ablation of myeloid MTHFD2 rendered mice more sensitive to septic shock and CCl4-induced acute hepatitis. Mechanistically, MTHFD2 restrained IKKα/β-NF-κB activation and macrophage inflammatory phenotype by scavenging reactive oxygen species through the generation of NADPH. Our study reveals MTHFD2 as a "self-control" mechanism in macrophage-med...
Source: Journal of Immunology - February 26, 2024 Category: Allergy & Immunology Authors: Yan Cui Zihan Li Lina Ni Sujun Yu Xiao Shan Penghui Hu Zemin Ji Weijia Jing Yanzhao Zhou Baochen Wang Hongyuan Dong Jinxue Zhou Keliang Xie Qiujing Yu Source Type: research

Correction: Myeloid Heterogeneity Mediates Acute Exacerbations of Pulmonary Fibrosis
J Immunol. 2024 Feb 26:ji2400069. doi: 10.4049/jimmunol.2400069. Online ahead of print.ABSTRACTWe thank Denise Stanford and the UAB Cystic Fibrosis Research Center Assay Core (The University of Alabama at Birmingham, Birmingham, AL) for assistance with microCT acquisition and image processing. Additional support was provided by the UAB Research and Development Program from the Cystic Fibrosis Foundation (Grant ROWE19RO [DAVIS]).PMID:38407351 | DOI:10.4049/jimmunol.2400069 (Source: Journal of Immunology)
Source: Journal of Immunology - February 26, 2024 Category: Allergy & Immunology Authors: Jennifer L Larson-Casey Komal Saleem Ranu Surolia Jyotsana Pandey Matthias Mack Veena B Antony Sandeep Bodduluri Surya P Bhatt Steven R Duncan A Brent Carter Source Type: research