美国MedImmune公司Alison A. Humbles研究小组和荷兰阿姆斯特丹大学Hergen Spits研究小组的一项最新研究，揭示了c-Kit阳性ILC2s表现出类似ILC3的特征，这可能与IL17介导的病理有关。这一研究成果于2019年8月发表在国际顶尖学术期刊《自然—免疫学》上。

研究人员识别了先天淋巴细胞亚型2(ILC2)分组人口,它可以转换成白介素-17 (IL-17)生成细胞 （NKp44 ILC3-样细胞）。c-Kit和CCR6定义这个ILC2亚群，表现出ILC3特性(包括RORγt)，并能在IL-1和IL-23作用下，使转换成IL-17-生成细胞。

该研究组还报道了转化生长因子在通过诱导IL23R、CCR6和Kit信使RNA在这些细胞中上调来促进c-Kit ILC2s转化为RORγt表达细胞中的作用。这个开关对这些基因是依赖于RORγt和GATA-3的差别。IL-4能够逆转这一事件，这种细胞因子发挥维持ILC2一致性的作用。值得注意的是，这种可塑性具有生理相关性，因为RORγt⁺ ILC2s的子集表达皮肤归巢受体CCR10，并且在银屑病患者受损皮肤中，IL17产生ILC3s的频率以ILC2s为代价而增加。

附：英文原文

Title: c-Kit-positive ILC2s exhibit an ILC3-like signature that may contribute to IL-17-mediated pathologies

Author: Jochem H. Bernink, Yoichiro Ohne, Marcel B. M. Teunissen, Jingya Wang, Jincheng Wu, Lisette Krabbendam, Christine Guntermann, Richard Volckmann, Jan Koster, Sophie van Tol, Ivan Ramirez, Yashaswi Shrestha, Menno A. de Rie, Hergen Spits, Xavier Romero Ros, Alison A. Humbles

Issue&Volume: Volume 20 Issue 8

Abstract: Here we identify a group 2 innate lymphoid cell (ILC2) subpopulation that can convert into interleukin-17 (IL-17)-producing NKp44 ILC3-like cells. c-Kit and CCR6 define this ILC2 subpopulation that exhibits ILC3 features, including RORt, enabling the conversion into IL-17-producing cells in response to IL-1 and IL-23. We also report a role for transforming growth factor- in promoting the conversion of c-Kit ILC2s into RORt-expressing cells by inducing the upregulation of IL23R, CCR6 and KIT messenger RNA in these cells. This switch was dependent on RORt and the downregulation of GATA-3. IL-4 was able to reverse this event, supporting a role for this cytokine in maintaining ILC2 identity. Notably, this plasticity has physiological relevance because a subset of RORt+ ILC2s express the skin-homing receptor CCR10, and the frequencies of IL-17-producing ILC3s are increased at the expense of ILC2s within the lesional skin of patients with psoriasis.

DOI: 10.1038/s41590-019-0423-0

Source:https://www.nature.com/articles/s41590-019-0423-0