<i>Tlr5</i>deficiency exacerbates lupus-like disease in the MRL/<i>lpr</i>mouse model

Abstract A leaky gut has been linked to numerous autoimmune disorders, including systemic lupus erythematosus (SLE). We had previously reported significant upregulation of anti-flagellin antibodies in the blood SLE patients and lupus-prone MRL/lpr mice, which led our hypothesis that a drove through bacterial flagellin-mediated activation toll-like receptor 5 (TLR5). Here, we investigated initiation progression lupus-like disease mice with global Tlr5 deletion generated by CRISPR-Cas9. Contrary would attenuate lupus, results showed exacerbation deficiency mice. significantly higher level proteinuria was observed −/−female compared +/−and +/+female littermates, suggesting aggravated glomerulonephritis deficiency. In kidney, increased renal infiltration activated conventional monocyte-derived dendritic cells. Spleen, mesenteric axillary/cervical lymph node body weight ratio were also −/−MRL/lpr +/+littermates, effects more pronounced fe malemice, impacted lymphoproliferation addition nephritis. are currently analyzing lymphoid tissues reveal potential cellular mechanisms. Notably, did not change existing either female or male Future studies will elucidate underlying mechanisms modulates functions exacerbate lupus.