Regulation of innate immune responses in the intestine

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Immune responses in the intestine must be tightly regulated to prevent unwanted inflammation against harmless antigens and commensal bacteria and yet allow for the induction of protective immunity to pathogens. A dysregulation of this balance results in abnormal immune responses leading to intestinal inflammation and allergy. The overall goal of my research is to improve our understanding of the regulation of immune responses in the intestine. The focus of the proposed research is to explore regulation of Toll-like receptors (TLR)-induced innate immune responses in Peyer's patches. TLRs are a class of receptors used by the immune system to detect microbial agents. TLRs are now known to be critical role in the initiation, development and regulation of innate and adaptive immune responses. We found that CpG DNA, an agonist for TLR9, strongly activates immune cells from blood, lymph nodes and spleen. However, CpG very poorly activated immune cells from Peyer's patches (PP) in the intestine, even though they express high levels of TLR9, suggesting that the poor responses are not due to lack of receptors. We found that resting PP cells spontaneously secreted high levels of an immunoregulatory cytokine IL-10, which suppressed innate immune responses in this tissue. We will now continue this investigation to fully establish how PP are involved in regulating intestinal innate immune responses. Understanding how TLR-induced immune responses are regulated in the intestine may contribute significantly in the rational development of oral vaccines and may direct therapeutic approaches to intestinal inflammatory conditions in animals.