Regulation of innate immune responses in the intestine

肠道内的免疫反应必须受到严格调节，以防止对无害抗原和共生细菌产生不必要的炎症，同时允许对病原体产生保护性免疫。这种平衡失调会导致免疫反应异常，导致肠道炎症和过敏。我研究的总体目标是提高我们对肠道免疫反应调节的理解。本研究的重点是探讨toll样受体（TLR）诱导的Peyer’s patches先天免疫应答的调控。tlr是一类被免疫系统用来检测微生物制剂的受体。目前已知tlr在先天和适应性免疫反应的启动、发展和调节中起关键作用。我们发现CpG DNA是TLR9的激动剂，能强烈激活来自血液、淋巴结和脾脏的免疫细胞。然而，CpG对肠道中来自Peyer’s patches （PP）的免疫细胞的激活非常差，尽管它们表达高水平的TLR9，这表明不良反应并非由于缺乏受体。我们发现休眠的PP细胞自发分泌高水平的免疫调节细胞因子IL-10，抑制该组织的先天免疫反应。我们现在将继续这项研究，以充分确定PP如何参与调节肠道先天免疫反应。了解tlr诱导的肠道免疫反应是如何调节的，可能对口服疫苗的合理开发有重要意义，并可能指导动物肠道炎症的治疗方法。

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.