Interleukin-2 regulation of mucosal inflammation

项目摘要 黏膜部位炎症失控是多发性慢性胃炎发生和发展的基础 人类疾病包括过敏、超敏、炎症性肠病(IBD)、癌症和移植物抗-1 宿主病(GVHD)，迫切需要开发新的方法来预防、限制或逆转 粘膜发炎。白介素2(IL-2)是一种对免疫学产生深远影响的多效性细胞因子 哺乳动物的耐受性和IL-2的调节目前正被开发为一种治疗方法 诊所。自从它被发现以来，大多数研究都集中在IL-2如何影响T细胞激活或 支持淋巴组织内的调节性T细胞(Tregs)。尽管取得了这些进展，但关键的细胞 IL-2在粘膜部位产生的来源和功能调节仍不清楚。这个 这项研究计划的基本重点是询问IL-2的新细胞来源， 严重影响哺乳动物胃肠道内的免疫平衡和炎症 (GI)肠道。我们将采用创新的方法和开发新的工具来定义 肠内稳态期间或肠道炎症和食物过敏后的粘膜IL-2。总而言之，结果 通过这些研究将确定新的细胞来源IL-2的调节和功能意义。 2在肠道内。这些发现将为正在进行的治疗方法提供关键的信息，以增强 IL-2，或促使开发新的易处理的策略以促进耐受性和控制 粘膜发炎。

PROJECT ABSTRACT Uncontrolled inflammation at mucosal sites underlies the pathogenesis and progression of multiple chronic human diseases including allergy, hypersensitivity, inflammatory bowel disease (IBD), cancer and graft-versus- host-disease (GVHD), and there is an urgent need to develop novel approaches to prevent, limit or reverse mucosal inflammation. Interleukin-2 (IL-2) is a pleiotropic cytokine that profoundly influences immunologic tolerance in mammals, and modulation of IL-2 is currently being developed as a therapeutic approach in the clinic. Since its discovery, a majority of research has focused on how IL-2 influences T cell activation or supports regulatory T cells (Tregs) within lymphoid tissues. Despite these advances, the critical cellular sources and functional regulation of IL-2 production at mucosal sites remains poorly defined. The fundamental focus of this research proposal is to interrogate novel cellular sources of IL-2 that critically influence immunologic homeostasis and inflammation within the mammalian gastrointestinal (GI) tract. We will employ innovative approaches and develop new tools to define the role and regulation of mucosal IL-2 during homeostasis or following intestinal inflammation and food allergy. Collectively, results from these studies will define the regulation and functional significance of novel cellular sources of IL- 2 within the intestine. These findings will critically inform ongoing therapeutic approaches to augment IL-2, or provoke the development of novel tractable strategies to promote tolerance and control mucosal inflammation.