Bruton’s tyrosine kinase impacts IgA repertoire and microbiome composition in non-obese diabetic mice

Abstract The microbiome has emerged as a contributor to type 1 diabetes (T1D), but how interactions between the and mucosal immune system lead or prevent T1D is not clear. Previously, we found that deletion of B cell signaling protein Bruton’s Tyrosine Kinase (BTK) selectively eliminates autoreactive cells autoantibodies, preventing development. However, discovered this disease protection microbiome-dependent, it disappears in cleaner facilities. We hypothesize disruption BTK-mediated receptor (BCR) promotes growth particular microbes are protective against by altering IgA production. Thus, objective study determine BTK-deficiency affects repertoire, shapes gut microbiome, synergistically prevents T1D. First, performed IgA-seq assess alters IgA-coating microbiota. Then, characterized microbiomes non-obese diabetic (NOD) mouse colonies living distinct environments using 16S sequencing conducted studies track altered ability coat microbiota small intestine colon. also significantly impacts composition NOD mice BTK-deficient have increased commensal diversity enrichment specific microbes. Based on these findings, conclude BCR production composition, with downstream effects pathogenesis. Supported grants from NIH (R01-DK-084246I) Veteran's Affairs (101-BX-002882)