In mice, a developmental window exists where microbial colonization of young mice leads to production of microbiota-specific T cells in the thymus. This window corresponds to microbiota stabilization which is critical for health and disease outcome later in life. In addition, mice with lupus and SLE patients exhibit intestinal dysbiosis with overgrowth and systemic translocation of gut pathobionts, which exacerbate lupus pathogenesis. The goals of this study are to assess how lupus development affects thymic generation of microbiota-specific T cells; identify the role of thymic microbiota-specific T cells in lupus pathogenesis; and test if systemic translocation of pathobionts expand thymic pathobiont-specific T cells and amplifies disease. This project is funded by the NIH Pathway to Independence Award K99/R00 (K99AR080207).

Mice with lupus and SLE patients exhibit intestinal dysbiosis with increased pathobionts, which exacerbate lupus pathogenesis. However, administration of a high-fiber diet or SCFAs to mice with lupus improves intestinal dysbiosis, intestinal barrier integrity, gut inflammation, and lupus outcome. These beneficial effects are observed if administration occurs before disease onset but are reduced if provided later in lupus development. The goals of this study are to assess if environmental factors affecting gut microbial communities have different effects in lupus pathogenesis; identify if intestinal inflammation drives lupus pathogenesis; and test if time of exposure is relevant for these effects.

Although the etiology of autoimmunity remains unknown, multiple autoimmune diseases, including SLE, are linked with intestinal dysbiosis. SLE patients exhibit intestinal dysbiosis characterized by overgrowth of gut pathobionts and loss of beneficial commensals as well as microbiota-specific T cell responses. The goals of this study are to identify changes in microbial communities and characterize microbiota-reactive T cells in SLE subsets sorted by sex, race, and disease activity to discover lupus-related pathobionts and pathobiont-specific T cells.