Cai Yihua, Xue Feng, Fleming Chris, Yang Jie, Ding Chuanlin, Ma Yunfeng, Liu Min, Zhang Huang-ge, Zheng Jie, Xiong Na, Yan Jun
1] James Graham Brown Cancer Center, Department of Medicine and Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky 40202, USA [2].
1] Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China [2].
Nat Commun. 2014 Jun 9;5:3986. doi: 10.1038/ncomms4986.
Dermal IL-17-producing γδT cells have 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 that requires IL-1 signalling. Mice with deficiency of IL-1RI signalling 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.
产生白细胞介素-17的皮肤γδT细胞在皮肤炎症中起关键作用。然而，它们的发育和外周调节尚未完全阐明。在此，我们证明皮肤γδT细胞起源于胚胎胸腺，出生后经历稳态增殖，其TCR库具有多样性。Vγ6T细胞是真正的驻留细胞，但皮肤Vγ4T细胞的前体可能需要胸腺外环境来赋予皮肤归巢特性。胸腺Vγ6T细胞在皮肤γδT细胞重建方面比Vγ4更具竞争力，用Vγ6重建的TCRδ(-/-)小鼠在应用咪喹莫特后会出现银屑病样炎症。虽然白细胞介素-23和白细胞介素-1β都能促进Vγ4和Vγ6增殖，但Vγ4是产生白细胞介素-17的主要来源，这一过程需要白细胞介素-1信号传导。白细胞介素-1受体I信号缺陷的小鼠皮肤炎症明显减轻。这些研究揭示了皮肤Vγ6和Vγ4γδT细胞在发育需求和外周调节上的差异，暗示了一种可能参与皮肤炎症的新机制。
