Differential developmental requirement and peripheral regulation for dermal Vγ4 and Vγ6T17 cells in health and inflammation.
Differential developmental requirement and peripheral regulation for dermal Vγ4 and Vγ6T17 cells in health and inflammation.
复制标题
DOI：
10.1038/ncomms4986
复制
发表时间：
2014-06-09
影响因子：
16.6
通讯作者：
Yan J
中科院分区：
文献类型：
--
作者：
Cai Y;Xue F;Fleming C;Yang J;Ding C;Ma Y;Liu M;Zhang HG;Zheng J;Xiong N;Yan J
真皮产生il -17的γδT细胞在皮肤炎症中起关键作用。然而，它们的发展和外围调控尚未完全阐明。在这里，我们证明真皮γδT细胞从胚胎胸腺发育而来，并在出生后经历稳态增殖，具有多样化的TCR库。v - γ - 6t细胞是真正的常驻细胞，但真皮v - γ - 4t细胞的前体可能需要胸腺外环境才能印记皮肤归巢特性。胸腺v - γ - 6t细胞在真皮γ - δ t细胞重建中比v - γ - 4更具竞争性，用v - γ - 6重建的TCRδ - / -小鼠在使用imq后出现牛皮癣样炎症。虽然IL-23和IL-1β都能促进v - γ - 4和v - γ - 6的增殖，但v - γ - 4是IL-17产生的主要来源，而IL-17的产生需要IL-1信号传导。缺乏IL-1RI信号的小鼠皮肤炎症明显减轻。这些研究揭示了真皮Vγ6和Vγ4 γδT细胞的不同发育需求和外周调节，暗示了一种可能参与皮肤炎症的新机制。
Dermal IL-17-producing γδT cells play a critical role in skin inflammation. However, their development and peripheral regulation have not been fully elucidated. Here we demonstrate that dermal γδT cells develop from the embryonic thymus and undergo homeostatic proliferation after birth with diversified TCR repertoire. Vγ6T cells are bona fide resident but precursors of dermal Vγ4T cells may require extrathymic environment for imprinting skin homing properties. Thymic Vγ6T cells are more competitive than Vγ4 for dermal γδT cell reconstitution and TCRδ−/− mice reconstituted with Vγ6 develop psoriasis-like inflammation after IMQ-application. Although both IL-23 and IL-1β promote Vγ4 and Vγ6 proliferation, Vγ4 are the main source of IL-17 production, which requires IL-1 signaling. Mice with deficiency of IL-1RI signaling have significantly decreased skin inflammation. These studies reveal a differential developmental requirement and peripheral regulation for dermal Vγ6 and Vγ4 γδT cells, implying a new mechanism that may be involved in skin inflammation.