c-Kit-positive ILC2s exhibit an ILC3-like signature that may contribute to IL-17-mediated pathologies
c-Kit-positive ILC2s exhibit an ILC3-like signature that may contribute to IL-17-mediated pathologies
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DOI：
10.1038/s41590-019-0423-0
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发表时间：
2019-08-01
影响因子：
30.5
通讯作者：
Humbles, Alison A.
中科院分区：
文献类型：
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作者：
Bernink, Jochem H.;Ohne, Yoichiro;Humbles, Alison A.
在这里，我们确定了第2组先天淋巴细胞（ILC 2）亚群，可以转化为白细胞介素-17（IL-17）-生产NKp 44（-）ILC 3样细胞。c-Kit和CCR 6定义了这种ILC 2亚群，其表现出ILC 3特征，包括ROR γ t，能够响应IL-1 β和IL-23转化为IL-17产生细胞。我们还报道了转化生长因子β通过诱导IL 23 R、CCR 6和KIT信使RNA在这些细胞中的上调，在促进c-Kit-ILC 2转化为ROR γ t表达细胞中的作用。这种转换依赖于ROR γ t和加塔-3的下调。IL-4能够逆转该事件，支持该细胞因子在维持ILC 2身份中的作用。值得注意的是，这种可塑性具有生理相关性，因为ROR γ t（+）ILC 2的子集表达皮肤归巢受体CCR 10，并且在银屑病患者的病变皮肤内，以ILC 2为代价增加了产生IL-17的ILC 3的频率。
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 ROR gamma t, enabling the conversion into IL-17-producing cells in response to IL-1 beta and IL-23. We also report a role for transforming growth factor-beta in promoting the conversion of c-Kit-ILC2s into ROR gamma t-expressing cells by inducing the upregulation of IL23R, CCR6 and KIT messenger RNA in these cells. This switch was dependent on ROR gamma t 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 ROR gamma t(+) 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.