Distinct Gene Regulatory Pathways for Human Innate versus Adaptive Lymphoid Cells.
Distinct Gene Regulatory Pathways for Human Innate versus Adaptive Lymphoid Cells.
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DOI：
10.1016/j.cell.2016.04.014
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发表时间：
2016-05-19
期刊：
影响因子：
64.5
通讯作者：
Oltz EM
中科院分区：
文献类型：
--
作者：
Koues OI;Collins PL;Cella M;Robinette ML;Porter SI;Pyfrom SC;Payton JE;Colonna M;Oltz EM
先天淋巴样细胞（ILCs）在粘膜组织中充当哨兵，感知可溶性炎症介质的释放，通过细胞因子的分泌迅速传达危险，并作为组织稳态的守护者。尽管在模式生物中对ilc进行了广泛的研究，但对人类中的这些“第一反应者”知之甚少，特别是它们的谱系和与细胞因子分泌T辅助细胞（Th）对应细胞的功能亲缘关系。在这里，我们报告了来自粘膜环境的四种人类ILC - Th对偶体的基因调控回路，揭示了每个ILC亚群作为Th和循环自然杀伤细胞的独特谱系而分化，但与Th对偶体共享致力于功能极化的回路。超级增强子划分了每个谱系中的细胞识别基因队列，揭示了特征细胞因子的新调节模式，可能赋予ilc重要功能的新分子，以及ILC-Th亚群中自身免疫性疾病SNP关联的潜在机制。
Innate lymphoid cells (ILCs) serve as sentinels in mucosal tissues, sensing release of soluble inflammatory mediators, rapidly communicating danger via cytokine secretion, and functioning as guardians of tissue homeostasis. Although ILCs have been studied extensively in model organisms, little is known about these “first responders” in humans, especially their lineage and functional kinships to cytokine-secreting T helper (Th) cell counterparts. Here, we report gene regulatory circuitries for four human ILC–Th counterparts derived from mucosal environments, revealing that each ILC subset diverges as a distinct lineage from Th and circulating natural killer cells, but shares circuitry devoted to functional polarization with their Th counterparts. Super-enhancers demarcate cohorts of cell identity genes in each lineage, uncovering new modes of regulation for signature cytokines, new molecules that likely impart important functions to ILCs, and potential mechanisms for autoimmune disease SNP associations within ILC–Th subsets.