BATF regulates innate lymphoid cell hematopoiesis and homeostasis.

BATF regulates innate lymphoid cell hematopoiesis and homeostasis.
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DOI:
10.1126/sciimmunol.aaz8154
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发表时间:
2020-12-04
期刊:
影响因子:
24.8
通讯作者:
Kim CH
Kim CH
中科院分区:
医学1区
文献类型:
--
作者:
Liu Q;Kim MH;Friesen L;Kim CH

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早期造血祖细胞经历复杂的发育过程,成为定向先天淋巴样细胞(ILC)祖细胞,并最终在外周成熟ILC亚群。碱性亮氨酸拉链ATF样转录因子(BasicLeucineZipperATF-Liketranscriptionfactor,Batf)在淋巴细胞生物学中起重要作用。我们在这里报告,Batf调节骨髓ILC祖细胞的产生和外周ILC的维持。在α-淋巴祖细胞(αLP)阶段的ILC发育过程中,响应于细胞因子IL-7诱导Batf的表达。作为一种潜在的机制,上调的Batf结合并激活Nfil 3基因的转录以促进ILC造血。Batf是维持骨髓中早期和晚期ILC祖细胞以及大多数外周组织中成熟ILC 1、ILC 2、ILC 3和NK细胞的正常数量所必需的。Batf缺乏导致ILC淋巴细胞减少症,导致ILC对炎性细胞因子的反应缺陷和对肠道细菌感染的免疫缺陷。因此,Batf在骨髓造血、外周稳态和ILC的效应器功能中发挥着关键作用。Batf支持外周组织中ILC祖细胞和NK、ILC 1、ILC 2和ILC 3的最佳群体的分化。
Early hematopoietic progenitors undergo sophisticated developmental processes to become committed innate lymphoid cell (ILC) progenitors and ultimately mature ILC subsets in the periphery. Basic leucine zipper ATF-Like transcription factor (Batf) plays important roles in lymphocyte biology. We report here that Batf regulates the production of bone marrow ILC progenitors and maintenance of peripheral ILCs. The expression of Batf is induced during ILC development at the α-lymphoid progenitor (αLP) stage in response to the cytokine IL-7. As a potential mechanism, upregulated Batf binds and activates transcription of the Nfil3 gene to promote ILC hematopoiesis. Batf is necessary to maintain normal numbers of early and late ILC progenitors in the bone marrow and mature ILC1, ILC2, ILC3, and NK cells in most peripheral tissues. Batf deficiency causes ILC lymphopenia, leading to defective ILC responses to inflammatory cytokines and defective immunity to enteric bacterial infections. Thus, Batf plays critical roles in bone marrow hematopoiesis, peripheral homeostasis, and effector functions of ILCs. Batf supports differentiation of ILC progenitors and optimal population of NK, ILC1, ILC2, and ILC3 in peripheral tissues.
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