Cytokine mediated mechanisms In the immunopathogenesis of inflammatory bowel diseases

炎症性肠病免疫发病机制中的细胞因子介导机制

• 批准号: 206954305
• 负责人: Professor Dr. Christoph Becker
• 金额: --
• 依托单位: Medizinische Klinik 1 - Gastroenterologie, Pneumologie und Endokrinologie
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/206954305?language=en
• 关键词: Cytokine; mediated; mechanisms; immunopathogenesis; inflammatory

Substantial amounts of cytokines are produced by various cell types during inflammatory flares in IBD patients. While proinflammatory cytokines initiate and sustain the inflammatory process, anti-inflammatory cytokines control intestinal immune responses and suppress inflammation. Only recently, tissue-regulatory cytokines secreted by non-hematopoletic cells such as IL-33 emerged as key innate players in the establishment of barrier Integrity and in the context of gut inflammation. The cytokine IL-33 is strongly upregulated in IBD. However, studies are conflicting and the precise role of this alarmin-like protein in the context of IBD remains to be fully characterized. Data from the literature as well as our own preliminary data indicate that IL-33 might be gut protective by orchestrating cellular functions in different cell types, such as innate lymphoid cells (ILC) and intestinal epithelial cells (lEC). We therefore aim to analyze the cell-specific functions of IL-33 on different intestinal cell compartments in the context of intestinal inflammation. Based on preliminary data, we will study, how IL-33 regulates lEC and type II innate lymphoid cell (ILC2) functions in the course of intestinal inflammation in mice as well as in IBD patients. Finally we will investigate if and how IL-33 is involved in ILC2 - lEC cellular crosstalk. In summary we aim at a better understanding of the molecular mechanisms of IL-33 function to identify gut protective pathways that could be targeted for future therapeutic intervention.

IBD患者的炎症性耀斑期间，各种细胞类型产生大量的细胞因子。促炎细胞因子启动并维持炎症过程，但抗炎细胞因子控制肠道免疫反应并抑制炎症。直到最近，在建立屏障完整性和肠道炎症的背景下，非移动性细胞（例如IL-33）分泌的组织调节细胞因子才成为关键的先天参与者。 IBD中的细胞因子IL-33强烈上调。但是，研究是矛盾的，在IBD背景下，这种警报蛋白的确切作用仍然有待充分表征。来自文献的数据以及我们自己的初步数据表明，IL-33可能通过在不同细胞类型的细胞功能（例如先天淋巴样细胞（ILC）和肠上皮细胞（LEC））中策划细胞功能来保护IL-33。因此，我们旨在分析IL-33在肠道炎症背景下IL-33对不同肠细胞室的细胞特异性功能。根据初步数据，我们将研究IL-33如何在小鼠以及IBD患者的肠炎过程中调节LEC和II型先天淋巴样细胞（ILC2）功能。最后，我们将研究IL -33是否以及如何参与ILC2 -LEC细胞串扰。总而言之，我们旨在更好地了解IL-33功能的分子机制，以识别可以针对未来治疗干预的肠道保护途径。