Differential Regulation and Function of Skin Innate Lymphoid Cells in Homeostasis and Inflammation

摘要 皮肤经常受到环境代理人的攻击。各种免疫细胞驻留在 以保护皮肤免受攻击。先天淋巴样细胞(ILCs)是一类 最近发现的先天淋巴细胞优先集中在屏障组织中 例如用于局部保护的皮肤，但它们也可能参与促进皮肤 炎症性疾病如果调节失调的话。了解特定于皮肤的定位和 先天淋巴样细胞的功能被调节是帮助设计 针对特定先天淋巴细胞群体的策略，用于治疗目的。我们的 先前的研究发现，健康皮肤中的大多数ILC表达一种皮肤- 特异性趋化因子受体CCR10。此外，我们发现皮肤特异性CCR10+ 在动态平衡条件下，皮肤引流淋巴结(SLN)产生ILC 在皮肤相关CD207+树突状细胞(DC)的帮助下，并依赖CCR10 它们在皮肤中的定位，在那里它们调节调节和效应T细胞以 促进皮肤免疫动态平衡。处于免疫调节失调或炎症状态 条件下，CCR10+ILCs的生成减少而增加 皮肤中CCR10+ILCs分化为CCR10-ILCs，提示CCR10+ 而CCR10-ILCs在皮肤内稳态和炎症中的作用不同。在……里面 在这个应用中，我们将确定潜在的细胞和分子机制 皮肤特异性ILCs在动态平衡和炎症中的产生和功能。

Summary Skin is under frequent assaults from environmental agents. Various immune cells reside in the skin to protect against the assaults. Innate lymphoid cells (ILCs) are a family of recently identified innate lymphocytes that are preferentially enriched in barrier tissues such as the skin for local protection but they could be also involved in promoting the skin inflammatory diseases if dysregulated. Understanding how skin-specific localization and function of the innate lymphoid cells are regulated is critical in helping to design the strategy targeting specific innate lymphocyte populations for therapeutic purposes. Our previous study has found that the majority of ILCs in the healthy skin expressed a skin- specific chemokine receptor CCR10. In addition, we found that the skin-specific CCR10+ ILCs were generated in skin-draining lymph nodes (sLNs) under homeostatic conditions with help of skin-associated CD207+ dendritic cells (DCs) and depended on CCR10 for their localization in the skin, where they regulate regulatory and effector T cells to promote skin immune homeostasis. Under immune dysregulatory or inflammatory conditions, generation of CCR10+ ILCs was reduced while there was increased differentiation of CCR10+ ILCs into CCR10- ILCs in the skin, suggesting that CCR10+ and CCR10- ILCs are differentially involved in the skin homeostasis and inflammation. In this application, we will determine cellular and molecular mechanisms underlying generation and function of skin-specific ILCs in homeostasis and inflammation.