Tlr9 deficiency in B cells leads to obesity by modulating the immune system and gut microbiota

We generate B-cell-specific Tlr9-deficient (Tlr9fl/fl/Cd19Cre+/-, KO) B6 mice and model obesity using a high-fat diet. Compared with control mice, B cell Tlr9-deficient mice exhibited increased weight gain, impaired glucose and insulin tolerance, reduced IL-10-producing B cells and increased inflammation in fat tissues. Tlr9 deficiency affected B cell differentiation, immunoglobulin levels, and T cell subsets. Furthermore, altered gut microbiota in B-cell-specific Tlr9-deficient mice led to a pro-inflammatory status in gut associated lymphoid tissues and glucose metabolism dysregulation. Using 16S rRNA sequencing we report altered gut microbial communities in the KO mice. Indeed, a reduction in Lachnospiraceae, may play a key role in the observed metabolic phenotypes in KO mice. Also, We identify an important network involving Tlr9, Irf4 and Il-10. Overall design: We generate B-cell-specific Tlr9-deficient (Tlr9fl/fl/Cd19Cre+/-, KO) B6 mice and model obesity using a high-fat diet. Compare the body weight and immune phenotype then the gut microbiota between the KO mice and Ctr mice. Then use germ free mice and Rag1-/- mice to confirm the function of Tlr9 deficiency on B cells.Finally we would like to compare the effect of Tlr9 deficiency in B cells on molecular level, then we did RNA-seq.