Non-redundant functions of type 3 innate lymphoid cells in mucosal immunity

3型先天淋巴样细胞（ILC3）在宿主生理学中执行多种功能。然而，其中大多数 在T细胞耗竭的背景下已经阐明了这些功能。有一个广泛的重叠监管 ILC3和Th17细胞之间的功能网络以及这两种细胞类型如何有助于免疫 还不清楚ILC3非冗余功能的鉴定受到缺乏ILC3耗竭的阻碍 保持正常T细胞发育和分化的模型。为了填补这一知识空白，我们 创建了第一个模型，其中ILC3的发展被阻止，但B和T细胞的发展和T细胞 分化正常。使用该模型，我们证明了ILC 3在粘膜中的非冗余功能 保护免受肠道病原体的侵害。我们将研究这种保护的具体机制， 以及鉴定ILC3的新的T细胞非依赖性功能。此外，我们将解除LTi的作用， 淋巴结和派伊尔集合淋巴结的发育起成人固有层ILC3的作用。我们还将 研究ILC3在调节肠道微生物群的稳态中的作用。总的来说，我们的研究 将阐明控制非冗余ILC3功能的细胞和分子机制， 维持健康的肠道和调节感染性肠道炎症。我们希望结果能引领 开发针对ILC3和Th17细胞的更特异性策略，以改善肠道免疫功能， 免疫失衡或预防病理性肠道炎症。

Type 3 innate lymphoid cells (ILC3) perform multiple functions in host physiology. However, most of these functions have been elucidated in the context of T cell depletion. There is an extensive overlap of regulatory and functional networks between ILC3 and Th17 cells and how these two cell types contribute to immunity is unclear. Identification of non-redundant functions of ILC3 has been impeded by the lack of ILC3 depletion models that preserve normal T cell development and differentiation. To address this gap in knowledge, we created the first model in which ILC3 development is prevented, but B and T cell development and T cell differentiation is normal. Using this model we demonstrate a non-redundant function of ILC3 in mucosal protection against an intestinal pathogen. We will examine the specific mechanism of this protection, as well as identify novel T cell-independent functions of ILC3. Moreover, we will uncouple the role of LTi in lymph node and Peyer’s patch development from the role of adult lamina propria ILC3. We will also investigate the role of ILC3 in regulating homeostasis with the intestinal microbiota. Overall, our studies will elucidate the cellular and molecular mechanisms controlling non-redundant ILC3 functions in both maintaining a healthy gut and regulating infectious intestinal inflammation. We expect the results to lead to the development of more specific strategies for targeting ILC3 and Th17 cells to improve intestinal immune dysbalance or prevent pathologic intestinal inflammation.