Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes
Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes
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Hobit和Blimp1指示淋巴细胞组织驻留的通用转录程序
DOI：
10.1126/science.aad2035
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发表时间：
2016-04-22
期刊：
影响因子：
56.9
通讯作者：
van Gisbergen, Klaas P. J. M.
中科院分区：
文献类型：
--
作者：
Mackay, Laura K.;Minnich, Martina;van Gisbergen, Klaas P. J. M.
组织驻留记忆T（Trm）细胞永久定位于病原体进入的门户，在那里它们提供立即保护以防止再感染。为了加强组织保留，Trm细胞上调CD 69并下调与组织流出相关的分子;然而，尚未鉴定Trm特异性转录调节因子。在这里，我们发现转录因子Hobit在Trm细胞中特异性上调，并与相关的Blimp 1一起介导小鼠皮肤，肠道，肝脏和肾脏中Trm细胞的发育。Hobit-Blimp 1转录模块也是其他组织驻留淋巴细胞群体所必需的，包括自然杀伤T（NKT）细胞和肝脏驻留NK细胞，所有这些细胞都有一个共同的转录程序。我们的研究结果确定Hobit和Blimp 1作为中央监管机构的这个通用程序，指示组织保留在不同的组织居民淋巴细胞群体。
Tissue-resident memory T (Trm) cells permanently localize to portals of pathogen entry, where they provide immediate protection against reinfection. To enforce tissue retention, Trm cells up-regulate CD69 and down-regulate molecules associated with tissue egress; however, a Trm-specific transcriptional regulator has not been identified. Here, we show that the transcription factor Hobit is specifically up-regulated in Trm cells and, together with related Blimp1, mediates the development of Trm cells in skin, gut, liver, and kidney in mice. The Hobit-Blimp1 transcriptional module is also required for other populations of tissue-resident lymphocytes, including natural killer T (NKT) cells and liver-resident NK cells, all of which share a common transcriptional program. Our results identify Hobit and Blimp1 as central regulators of this universal program that instructs tissue retention in diverse tissue-resident lymphocyte populations.