Serine Phosphorylation of the STAT1 Transactivation Domain Promotes Autoreactive B Cell and Systemic Autoimmunity Development.

Serine Phosphorylation of the STAT1 Transactivation Domain Promotes Autoreactive B Cell and Systemic Autoimmunity Development. J Immunol. 2020 Apr 06;: Authors: Chodisetti SB, Fike AJ, Domeier PP, Schell SL, Mockus TE, Choi NM, Corradetti C, Hou B, Atkins HM, Caricchio R, Decker T, Lukacher AE, Olsen N, Rahman ZSM Abstract Although STAT1 tyrosine-701 phosphorylation (designated STAT1-pY701) is indispensable for STAT1 function, the requirement for STAT1 serine-727 phosphorylation (designated STAT1-pS727) during systemic autoimmune and antipathogen responses remains unclear. Using autoimmune-prone B6.Sle1b mice expressing a STAT1-S727A mutant in which serine is replaced by alanine, we report in this study that STAT1-pS727 promotes autoimmune Ab-forming cell (AFC) and germinal center (GC) responses, driving autoantibody production and systemic lupus erythematosus (SLE) development. In contrast, STAT1-pS727 is not required for GC, T follicular helper cell (Tfh), and Ab responses to various foreign Ags, including pathogens. STAT1-pS727 is also not required for gut microbiota and dietary Ag-driven GC and Tfh responses in B6.Sle1b mice. By generating B cell-specific bone marrow chimeras, we demonstrate that STAT1-pS727 plays an important B cell-intrinsic role in promoting autoimmune AFC, GC, and Tfh responses, leading to SLE-associated autoantibody production. Our analysis of the TLR7-accelerated B6.Sle1b.Yaa SLE disease model expressing a STAT1-S727A mutant re...
Source: Journal of Immunology - Category: Allergy & Immunology Authors: Tags: J Immunol Source Type: research

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CONCLUSION: The IL-17 rs2275913 A allele and A/A genotype were associated with high IL-17 serum levels and may contribute to susceptibility to JSLE and the development of LN in Egyptian children and adolescents. However, no significant association was evident between the studied IL-17A SNPs and other clinical phenotypes, disease activity scores or laboratory profile of JSLE. PMID: 32380889 [PubMed - as supplied by publisher]
Source: Lupus - Category: Rheumatology Authors: Tags: Lupus Source Type: research
Systemic lupus erythematosus (SLE) is a chronic systematic autoimmune disease. Current methods of diagnosing SLE or evaluating its activity are complex and expensive. Numerous studies have suggested that neutrophil-to-lymphocyte ratio (NLR) is closely correlated with the presence of SLE and its activity, suggesting that it may serve as a diagnostic and monitoring indicator for SLE. Therefore, we performed a meta-analysis to systematically assess the association between NLR and SLE. We performed a literature search until 12 April 2019 in the PubMed, Web of Science, and China National Knowledge Infrastructure databases. Cros...
Source: Clinics - Category: General Medicine Source Type: research
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Source: Science Translational Medicine - Category: Biomedical Science Authors: Tags: Research Articles Source Type: research
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Source: BMC Nephrology - Category: Urology & Nephrology Authors: Tags: Research article Source Type: research
Authors: Sharma M, Vignesh P, Tiewsoh K, Rawat A Abstract Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organ systems, characterized by the production of autoantibodies. Numerous mechanisms contribute to the pathogenesis and development of autoantibodies and autoimmunity in SLE. One of the most important mechanisms is the defective function of the early complement components that are involved in clearing the immune-complexes and apoptotic debris. Major evidence supporting this hypothesis is the development of severe forms of lupus in individuals with monogenic defects ...
Source: Expert Review of Clinical Immunology - Category: Allergy & Immunology Tags: Expert Rev Clin Immunol Source Type: research
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Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
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Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research
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Source: Immunity, Inflammation and Disease - Category: Allergy & Immunology Authors: Tags: ORIGINAL RESEARCH Source Type: research
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Source: Clinical Immunology - Category: Allergy & Immunology Authors: Tags: Clin Immunol Source Type: research
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Source: Arthritis Research and Therapy - Category: Rheumatology Authors: Tags: Research article Source Type: research
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