Differentiation of Type 1 ILCs from a Common Progenitor to All Helper-like Innate Lymphoid Cell Lineages
Differentiation of Type 1 ILCs from a Common Progenitor to All Helper-like Innate Lymphoid Cell Lineages
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DOI：
10.1016/j.cell.2014.03.030
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发表时间：
2014-04-10
期刊：
影响因子：
64.5
通讯作者：
Diefenbach, Andreas
中科院分区：
文献类型：
--
作者：
Klose, Christoph S. N.;Flach, Melanie;Diefenbach, Andreas
先天性淋巴细胞（ILC）是最近被认可的一组淋巴细胞，在保护上皮屏障免受感染和维持器官稳态方面具有重要功能。 ILC 已被分为三个不同的组，其转录回路和效应器功能与各种 T 辅助细胞亚群惊人地相似。在这里，我们鉴定了所有表达白细胞介素7受体的“辅助样”ILC谱系的一个共同的、表达Id2的祖细胞，即CHILP。有趣的是，CHILP 分化为 ILC2 和 ILC3 谱系，但未分化为被认为是 ILC1 子集的传统自然杀伤 (cNK) 细胞。相反，CHILP 产生了一种特殊的 NKp46(+) IL-7R alpha(+) ILC 谱系，该谱系需要 T-bet 进行规范，并且与 cNK 细胞或其他 ILC 谱系不同。这种 ILC1 共同产生高水平的 IFN-γ 和 TNF，并防止细胞内寄生虫弓形虫的感染。我们的数据显着增进了我们对 ILC 分化的理解，并为保护屏障表面免受细胞内感染的新 ILC 谱系提供了证据。
Innate lymphoid cells (ILCs) are a recently recognized group of lymphocytes that have important functions in protecting epithelial barriers against infections and in maintaining organ homeostasis. ILCs have been categorized into three distinct groups, transcriptional circuitry and effector functions of which strikingly resemble the various T helper cell subsets. Here, we identify a common, Id2-expressing progenitor to all interleukin 7 receptor-expressing, "helper-like" ILC lineages, the CHILP. Interestingly, the CHILP differentiated into ILC2 and ILC3 lineages, but not into conventional natural killer (cNK) cells that have been considered an ILC1 subset. Instead, the CHILP gave rise to a peculiar NKp46(+) IL-7R alpha(+) ILC lineage that required T-bet for specification and was distinct of cNK cells or other ILC lineages. Such ILC1s coproduced high levels of IFN-gamma and TNF and protected against infections with the intracellular parasite Toxoplasma gondii. Our data significantly advance our understanding of ILC differentiation and presents evidence for a new ILC lineage that protects barrier surfaces against intracellular infections.