Role of Immunoglobulin A (IgA)-gut microbiota interaction in systemic lupus erythematosus 4398
Year: 2025
Type: article
Abstract: Description Systemic lupus erythematosus (SLE) is an autoimmune disorder that affects multiple organs. Women show higher SLE incidence rate than men. Our preclinical studies showed that pro-inflammatory events initiated in the gut mucosa contribute to lupus autoimmunity. We also showed that the abundance and nuclear antigen (nAg) reactivity of IgA are higher in fecal samples from lupus-prone mice. Depletion of gut microbiota diminished the fecal IgA abundance and nAg reactivity. Therefore, we hypothesized that gut microbiota-IgA interaction contributes to systemic autoimmune progression and lupus pathogenesis. We tested this hypothesis by monitoring newly generated NZM2328-IgA-/- mouse model. We found that IgA deficiency, compared to wild-type (WT) mice, protects both male and female mice from severe nephritis. Paradoxically, dsDNA and nucleohistone reactive IgM and IgG antibody levels were significantly higher in NZM2328-IgA-/- mice. However, our preliminary observations suggest that expression levels of pro- and anti- inflammatory cytokines are comparable in WT and IgA-/- mice. Our ongoing studies are focused on understanding the role of gut microbiota in IgA-deficiency associated disease protection and the mechanisms by which IgA-gut microbiota interaction is contributing to autoimmunity. Overall, these systematic studies will, for the first time, address the role of IgA-gut microbiota interaction in lupus autoimmunity. Funding Sources NIH/NIAID R01AI138511 Topic Categories Mucosal and Regional Immunology (MUC)
Source: The Journal of Immunology
Authors: Jaisheela Vimali Irudhayaraj, Soumyabrata Roy, Ruchika Maurya, Samantha Webber, Ping Lu, Chenthamarakshan Vasu
Institution: Medical University of South Carolina
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4416449653
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