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

皮肤先天淋巴细胞在稳态和炎症中的差异调节和功能

• 批准号: 9898114
• 负责人: NA XIONG
• 金额: $ 29.9万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9898114
• 关键词: Address; Applications Grants; Atopic Dermatitis; Biological; CCL27 gene; Cells; Chemicals; Dendritic Cells; Development; Disease; Down-Regulation; Eragrostis; Family; Functional disorder; Future; GPR2 gene; Generations; Homeostasis; Homing; Human; Immune; Immune response; Immune system; In Vitro; Inflammation; Inflammatory; Inflammatory Response; Knock-in; Knock-in Mouse; Knock-out; Lead; Ligands; Lymphocyte; Lymphoid Cell; Mediator of activation protein; Molecular; Mus; Pathogenesis; Patients; Population; Process; Psoriasis; Rag1 Mouse; Regulation; Regulatory T-Lymphocyte; Role; Skin; Surface; T-Lymphocyte; Therapeutic; Tissues; assault; base; chemokine receptor; design; effector T cell; environmental agent; immune activation; immunoregulation; lymph nodes; mouse model; novel; novel therapeutics; prevent; receptor; response; skin disorder; skin lesion; skin organogenesis; transcription factor

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.

总结 皮肤经常受到环境因子的攻击。各种免疫细胞 保护自己免受攻击先天性淋巴样细胞（ILC）是一个家族， 最近发现的先天性淋巴细胞优先富集在屏障组织中， 如皮肤局部保护，但他们也可以参与促进皮肤 炎症性疾病，如果失调。了解特定于皮肤的定位和 先天淋巴细胞的功能受到调节，这对于帮助设计 靶向特定先天淋巴细胞群体的策略用于治疗目的。我们 之前的研究发现，健康皮肤中的大多数ILC表达皮肤- 特异性趋化因子受体CCR 10。此外，我们发现皮肤特异性CCR 10 + 在稳态条件下，皮肤引流淋巴结（sLN）中产生ILC 在皮肤相关的CD 207+树突状细胞（DC）的帮助下， 它们在皮肤中的定位，在那里它们调节调节和效应T细胞， 促进皮肤免疫稳态。免疫失调或炎症 条件下，CCR 10 + ILC的产生减少，而CCR 10 + ILC的产生增加。 CCR 10 + ILC在皮肤中分化为CCR 10-ILC，表明CCR 10 + ILC在皮肤中分化为CCR 10-ILC。 和CCR 10-ILC差异参与皮肤稳态和炎症。在 本申请，我们将确定细胞和分子机制， 在稳态和炎症中皮肤特异性ILC的产生和功能。