deficiency alters gut microbiota and ameliorates -mediated systemic autoimmunity in male mice.

NLRP12 has dual roles in shaping inflammation. We hypothesized that NLRP12 would modulate myeloid cells and T cell function to control systemic autoimmunity. Contrary to our hypothesis, the deficiency of in autoimmune-prone B6. mice ameliorated autoimmunity in males but not females. deficiency dampened B cell terminal differentiation, germinal center reaction, and survival of autoreactive B cells leading to decreased production of autoantibodies and reduced renal deposition of IgG and complement C3. In parallel, deficiency reduced the expansion of potentially pathogenic T cells, including double-negative T cells and T follicular helper cells. Furthermore, reduced pro-inflammatory innate immunity was observed, where the gene deletion decreased expansion of splenic macrophages and mitigated responses of bone marrow-derived macrophages and dendritic cells to LPS stimulation. Interestingly, deficiency altered the diversity and composition of fecal microbiota in both male and female B6/ mice. Notably, however, deficiency significantly modulated small intestinal microbiota only in male mice, suggesting that the sex differences in disease phenotype might be gut microbiota-dependent. Together, these results suggest a potential pathogenic role of NLRP12 in promoting systemic autoimmunity in males. Future studies will investigate sex-based mechanisms through which NLRP12 differentially modulates autoimmune outcomes.