Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany; Department of Medical Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University of Freiburg Medical Centre, Hermann-Herder-Strasse 11, 79104 Freiburg, Germany; Renal Division, University of Freiburg Medical Centre, Hugstetter Strasse 55, 79106 Freiburg, Germany.
Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany; Department of Medical Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University of Freiburg Medical Centre, Hermann-Herder-Strasse 11, 79104 Freiburg, Germany.
Cell. 2014 Apr 10;157(2):340-356. doi: 10.1016/j.cell.2014.03.030.
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-7Rα(+) 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-γ 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.
先天淋巴细胞(ILCs)是最近被发现的一组淋巴细胞,它们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。ILCs 已被分为三个不同的群体,其转录电路和效应功能与各种辅助性 T 细胞亚群惊人地相似。在这里,我们鉴定出一个共同的、表达 ID2 的祖细胞,它表达白细胞介素 7 受体(IL-7R),是所有“辅助样”ILC 谱系的 CHILP。有趣的是,CHILP 分化为 ILC2 和 ILC3 谱系,但不能分化为传统的自然杀伤(cNK)细胞,后者被认为是 ILC1 亚群的一部分。相反,CHILP 产生了一种特殊的 NKp46(+)IL-7Rα(+)ILC 谱系,该谱系需要 T-bet 来特化,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,并能抵抗细胞内寄生虫弓形虫的感染。我们的数据显著推进了我们对 ILC 分化的理解,并为一种新的 ILC 谱系提供了证据,该谱系能保护屏障表面免受细胞内感染。