Vγ4 γδ T Cells Provide an Early Source of IL-17A and Accelerate Skin Graft Rejection
Vγ4 γδ T Cells Provide an Early Source of IL-17A and Accelerate Skin Graft Rejection
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V gamma 4 gamma delta T 细胞提供 IL-17A 的早期来源并加速皮肤移植排斥
DOI：
10.1016/j.jid.2017.03.043
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发表时间：
2017-12-01
影响因子：
6.5
通讯作者：
He, Weifeng
中科院分区：
文献类型：
--
作者：
Li, Yashu;Huang, Zhenggen;He, Weifeng
激活的Gamma Delta T细胞已被证明可以加速同种异体移植排斥反应。然而，皮肤驻留的γ-增量T细胞及其亚群--V-Gamma 5(表皮)、V-Gamma 1和V-Gamma 4(真皮)--在皮肤移植排斥反应中的确切作用尚未确定。在这里，使用男性到女性的皮肤移植模型，我们证明了V-Gamma 4T细胞，而不是V-Gamma 1或V-Gamma 5 T细胞加速了皮肤移植排斥反应，并且IL-17A在V-Gamma 4 T细胞介导的皮肤移植排斥反应中是必不可少的。此外，我们还发现，无论是在皮肤移植物中还是在移植物周围的宿主表皮中，V-Gamma 4T细胞都是移植区域早期产生IL-17A所必需的。此外，趋化因子(C-C基序)配体20-趋化因子受体6途径是V-Gamma 4T细胞向移植区域募集所必需的，而IL-1β和IL-23均可诱导浸润性细胞产生IL-17A。最后，V-Gamma 4T细胞来源的IL-17A促进引流淋巴结中成熟树突状细胞的积聚，从而调节皮肤移植后的α-βT细胞功能。综上所述，我们的数据显示，V-Gamma 4T细胞通过提供IL-17A的早期来源来加速皮肤移植排斥反应。
Activated gamma delta T cells have been shown to accelerate allograft rejection. However, the precise role of skin-resident gamma delta T cells and their subsets-V gamma 5 (epidermis), V gamma 1, and V gamma 4 (dermis)-in skin graft rejection have not been identified. Here, using a male to female skin transplantation model, we demonstrated that V gamma 4 T cells, rather than V gamma 1 or V gamma 5 T cells, accelerated skin graft rejection and that IL-17A was essential for V gamma 4 T-cell-mediated skin graft rejection. Moreover, we found that V gamma 4 T cells were required for early IL-17A production in the transplanted area, both in skin grafts and in the host epidermis around grafts. Additionally, the chemokine (C-C motif) ligand 20-chemokine receptor 6 pathway was essential for recruitment of V gamma 4 T cells to the transplantation area, whereas both IL-1 beta and IL-23 induced IL-17A production from infiltrating cells. Lastly, V gamma 4 T-cell-derived IL-17A promoted the accumulation of mature dendritic cells in draining lymph nodes to subsequently regulate alpha beta T-cell function after skin graft transplantation. Taken together, our data reveal that V gamma 4 T cells accelerate skin graft rejection by providing an early source of IL-17A.