Development of microbiota-specific T cells during systemic autoimmunity 3776

Description Systemic lupus erythematosus or lupus is a prototypical autoimmune disease characterized by an uncontrolled immune response against self-antigens, leading to organ malfunction and systemic inflammation. In lupus, intestinal dysbiosis occurs, and these microbial alterations support dysregulated innate and adaptive responses. Notably, the expansion and differentiation of proinflammatory T cells are altered in response to dysbiosis. However, the role of microbiota-specific (Mb) T cells during systemic autoimmunity or if their development is altered in lupus has not been demonstrated. Using TLR7-dependent mouse models of lupus, segmented filamentous bacteria (SFB), and a tetramer approach to track SFB-specific T cells, we found that systemic inflammation and autoimmunity support the expansion of Mb-T cells in the thymus and peripheral tissues. In lupus, Mb-T cells differentiate into Th1 and follicular helper T cells in a tissue-specific manner, which shapes the production of systemic and mucosal antibodies. Alterations in dendritic cell traffic and enrichment were found, and they correlated to modulation in T and B cell expansion and development. Through adoptive transfers, we are actively assessing the role of Mb-T cells in lupus pathogenesis. Our data suggests systemic inflammation and autoimmunity support the development of microbiota-specific T cells, which can modulate inflammatory processes and antibody production. Funding Sources U.S. NIH Institute of Arthritis, Musculoskeletal & Skin Disease (4R00AR080207-03) Topic Categories Basic Autoimmunity (BA)