Regulation of innate immune responses in the intestine

肠道中的免疫反应必须受到严格的控制，以防止针对无害抗原和共生菌的不必要的炎症，同时允许诱导对病原体的保护性免疫。这种平衡的失调会导致异常的免疫反应，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。这项研究的重点是探索Toll样受体(TLR)在Peyer‘s斑块中诱导的先天性免疫反应的调节。TLRs是免疫系统用来检测微生物制剂的一类受体。目前已知TLRs在先天免疫反应和获得性免疫反应的启动、发展和调节中起着关键作用。我们发现TLR9的激动剂CpG DNA能强烈激活血液、淋巴结和脾的免疫细胞。然而，CpG很难激活肠道中Peyer‘s Patches(PP)的免疫细胞，尽管它们表达高水平的TLR9，这表明反应差并不是由于缺乏受体。我们发现，静息的PP细胞自发地分泌高水平的免疫调节细胞因子IL-10，这种细胞因子抑制了该组织的先天免疫反应。我们现在将继续这项研究，以全面确定PP是如何参与调节肠道先天免疫反应的。了解TLR诱导的免疫反应在肠道中是如何调节的，可能会对合理开发口服疫苗做出重大贡献，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.