Interestingly, colonization of former germ-free mice with only segmented filamentous bacteria has been shown to drive the production of normal levels of IgA [13]. Colonization of germ-free mice with a conventional microbiota activates many innate immune responses including antimicrobial peptides (AMPs) expressed by ECs [9, 14, 15]. In

turn, AMPs regulate the intestinal bacterial community [16]. The regulation of these epithelially expressed AMPs is dynamic and requires continuous exposure to bacteria [17]. Similarly, the host IgA response to endogenous bacteria is dynamic and dominated by the specific SIgA recognizing the dominating RAD001 solubility dmso species in the gut [18]. The relationship between the host and its gut microbiota is important for host physiology, and perturbations in this homeostatic relationship are associated with inflammatory bowel disease [19]. Failure to properly restrain the beneficial commensal bacteria to the gut lumen may be

Proteasome inhibitor an underlying cause of intestinal inflammation. Furthermore, dysbiosis has been shown to play a role in several immune-mediated extra-intestinal diseases, such as diabetes, allergy, and multiple sclerosis [20-22]. Here, we have investigated gut homeostasis when an important mediator of host protection against commensal microbes is missing. pIgR KO mice fail to transport dIgA and pentameric IgM to the gut lumen and are therefore

deficient in the formation of secretory antibodies [23, 24]. We found that colonic ECs in untreated pIgR KO mice expressed elevated levels of mRNAs encoding AMPs compared with untreated WT mice and these differences depended on the presence of intestinal bacteria. Furthermore, the composition of Protein tyrosine phosphatase the intestinal microbial community differed between pIgR KO mice and WT mice, and pIgR KO mice showed enhanced susceptibility to dextran sulfate sodium (DSS)-induced colitis in a conventional specific pathogen-free environment. Together, these findings show that although the absence of secretory antibodies can partly be compensated for by enhanced innate antimicrobial responses, mucosal homeostasis is disturbed in pIgR KO mice, making them more prone to intestinal inflammation. To identify how basic cellular functions of intestinal ECs might be altered in the absence of SIg, we isolated mRNA from colonic ECs of pIgR KO and WT mice and determined their expression profiles by Illumina microarray experiments. A comparison of the mRNA expression profiles of colonic ECs from the two genotypes of mice identified 208 genes with greater than twofold differential expression and a q-value < 0.05 (Fig. 1A, blue circle, and Supporting Information Table 1).