BTK Supports Gut Mucosal Immunity and Commensal Microbiome in Autoimmune Arthritis

Btk) deficiency eliminates autoreactive B cells while sparing normal humoral responses, but has not been studied in mucosal immunity. Commensal microbes are essential for arthritis in K/BxN mice, used here to examine how BTK-mediated signaling interfaces with the microbiome. Intestinal IgA was low and IgA coating of commensal bacteria was reduced by Btk-deficiency. IgA-seq showed a shift in microbes that are normally IgA-coated into the uncoated fraction in Btk-deficient mice. Thus, BTK supports normal intestinal IgA development, with downstream effects on the microbiome that may contribute to autoimmunity.