MyD88-dependent regulation of the polymeric immunoglobulin receptor by colonic microbes (40.5)

Abstract

Abstract Secretory IgA serves as the first line of antigen-specific immunity in the intestine, protecting against pathogens while preventing inflammation in response to commensal microbes. Intestinal epithelial cells (IEC) regulate IgA secretion by controlling expression of the polymeric immunoglobulin receptor (pIgR). Many pro- and anti-inflammatory factors, including pIgR, are transcriptional targets of Toll-like receptor (TLR) signaling in response to molecular patterns from resident microbes. MyD88 is an important TLR signaling adaptor that has been implicated in regulation of intestinal inflammation. To assess the role of MyD88 in IEC gene expression, we compared mRNA levels of pIgR, TNF, and two regulatory factors, A20 and MKP-1, in the small intestines and colons of wild-type and MyD88−/− mice. Gene expression was significantly higher in the colon than in the small intestine of all mice, correlating with the higher microbial load. In the colon, expression of all genes was significantly higher in wild-type than in MyD88−/−mice. We conclude that commensal microorganisms set the tone of intestinal gene expression through MyD88-dependent TLR signaling. Supported by Crohn’s & Colitis Foundation of America.