Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
The Francis Crick Institute, London, UK.
EMBO Rep. 2017 Nov;18(11):1957-1967. doi: 10.15252/embr.201744200. Epub 2017 Aug 30.
Pro-inflammatory interleukin (IL)-17-producing γδ (γδ17) T cells are thought to develop exclusively in the thymus during fetal/perinatal life, as adult bone marrow precursors fail to generate γδ17 T cells under homeostatic conditions. Here, we employ a model of experimental autoimmune encephalomyelitis (EAE) in which hematopoiesis is reset by bone marrow transplantation and demonstrate unequivocally that Vγ4 γδ17 T cells can develop in draining lymph nodes in response to innate stimuli. γδ T cells from IL-17 fate-mapping reporter mice that had never activated the locus acquire IL-17 expression upon stimulation with IL-1β and IL-23. Furthermore, IL-23R (but not IL-1R1) deficiency severely compromises the induction of γδ17 T cells in EAE, demonstrating the key role of IL-23 in the process. Finally, we show, in a composite model involving transfers of both adult bone marrow and neonatal thymocytes, that induced γδ17 T cells make up a substantial fraction of the total IL-17-producing Vγ4 T-cell pool upon inflammation, which attests the relevance of this novel pathway of peripheral γδ17 T-cell differentiation.
促炎细胞因子白细胞介素（IL）-17 产生的 γδ（γδ17）T 细胞被认为仅在胎儿/围生期的胸腺中发育，因为在稳态条件下，成人骨髓前体不能产生 γδ17 T 细胞。在这里，我们采用实验性自身免疫性脑脊髓炎（EAE）模型，其中通过骨髓移植重置造血，并明确证明 Vγ4 γδ17 T 细胞可以在引流淋巴结中响应先天刺激而发育。从未激活过 基因座的 IL-17 命运映射报告小鼠的 γδ T 细胞在受到 IL-1β 和 IL-23 刺激时获得 IL-17 表达。此外，IL-23R（但不是 IL-1R1）缺陷严重损害 EAE 中 γδ17 T 细胞的诱导，表明 IL-23 在该过程中的关键作用。最后，我们在涉及成年骨髓和新生胸腺细胞转移的组合模型中表明，诱导的 γδ17 T 细胞在炎症时构成总 IL-17 产生的 Vγ4 T 细胞池的相当大一部分，这证明了这种新型外周 γδ17 T 细胞分化途径的相关性。
