Regulation of innate immune responses in the intestine

肠道先天免疫反应的调节

• 批准号: 227402-2009
• 负责人: Mutwiri, George
• 金额: $ 2.04万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=504109
• 关键词: Regulation; innate; immune; responses; intestine

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.

肠道中的免疫反应必须受到严格的调节，以防止对无害抗原和肠道细菌的不必要的炎症，同时允许诱导对病原体的保护性免疫。这种平衡失调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。拟开展的研究的重点是探讨Toll样受体（TLR）诱导的先天性免疫反应在派尔集合淋巴结的调节。TLR是免疫系统用来检测微生物的一类受体。目前已知TLR在先天性和适应性免疫应答的启动、发展和调节中起关键作用。 我们发现，CpG DNA，TLR 9的激动剂，强烈激活血液，淋巴结和脾脏的免疫细胞。然而，CpG非常差地激活肠中来自派伊尔集合淋巴结（PP）的免疫细胞，即使它们表达高水平的TLR 9，这表明不良反应不是由于缺乏受体。我们发现静息PP细胞自发分泌高水平的免疫调节细胞因子IL-10，其抑制该组织中的先天性免疫应答。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诱导的免疫应答在肠道中的调节方式可能有助于合理开发口服疫苗，并可能指导动物肠道炎症的治疗方法。