THE ROLE OF BRUTON'S TYROSINE KINASE IN REGULATING GUT IMMUNE HOMEOSTASIS AND INFLAMMATION

Abstract

Inflammatory bowel disease (IBD) is a gut immune disorder driven by multiple genetic and environmental risk factors. Recently, a study reveals a high prevalence of IBD in patients with Bruton’s tyrosine kinase (BTK) gene deficiency. BTK mediates the signalling of various immune receptors. However, little is known about the regulatory role BTK plays in maintaining the gut immune system.

In this study, we show that BTK deficiency promotes colitis progression in a mouse model, which may not be caused by gut microbiota changes. We find that BTK deficiency associates with increased pro-inflammatory Th1 cells and reduced anti-inflammatory RORγt+ Tregs in the gut, likely accounting for the increased colitis risk. Moreover, we identify that both T cell-extrinsic and -intrinsic mechanisms may explain the enhanced Th1 response, because BTK-deficient dendritic cells exhibit enhanced production of IL-12, and BTK-deficient CD4+ T cells are more prone to differentiating into Th1 cells. Therefore, our findings uncover a critical role of BTK in regulating gut immune homeostasis and inflammation.