State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Chongqing Key Laboratory for Disease Proteomics, Chongqing, China.
Front Immunol. 2018 Jun 4;9:1099. doi: 10.3389/fimmu.2018.01099. eCollection 2018.
Wound healing is a complex and dynamic process that progresses through the distinct phases of hemostasis, inflammation, proliferation, and remodeling. Both inflammation and re-epithelialization, in which skin γδ T cells are heavily involved, are required for efficient skin wound healing. Dendritic epidermal T cells (DETCs), which reside in murine epidermis, are activated to secrete epidermal cell growth factors, such as IGF-1 and KGF-1/2, to promote re-epithelialization after skin injury. Epidermal IL-15 is not only required for DETC homeostasis in the intact epidermis but it also facilitates the activation and IGF-1 production of DETC after skin injury. Further, the epidermal expression of IL-15 and IGF-1 constitutes a feedback regulatory loop to promote wound repair. Dermis-resident Vγ4 T cells infiltrate into the epidermis at the wound edges through the CCR6-CCL20 pathway after skin injury and provide a major source of IL-17A, which enhances the production of IL-1β and IL-23 in the epidermis to form a positive feedback loop for the initiation and amplification of local inflammation at the early stages of wound healing. IL-1β and IL-23 suppress the production of IGF-1 by DETCs and, therefore, impede wound healing. A functional loop may exist among Vγ4 T cells, epidermal cells, and DETCs to regulate wound repair.
伤口愈合是一个复杂而动态的过程，经历止血、炎症、增殖和重塑等不同阶段。皮肤 γδ T 细胞大量参与的炎症和再上皮化对于有效的皮肤伤口愈合是必需的。位于鼠类表皮的树突状表皮 T 细胞（DETCs）在皮肤损伤后被激活，分泌表皮细胞生长因子，如 IGF-1 和 KGF-1/2，以促进再上皮化。表皮 IL-15 不仅是 DETC 在完整表皮中维持稳态所必需的，而且还促进皮肤损伤后 DETC 的激活和 IGF-1 的产生。此外，表皮中 IL-15 和 IGF-1 的表达构成了一个反馈调节环，以促进伤口修复。皮肤损伤后，真皮驻留的 Vγ4 T 细胞通过 CCR6-CCL20 途径浸润到伤口边缘的表皮中，并提供大量的 IL-17A，增强表皮中 IL-1β 和 IL-23 的产生，形成一个正反馈环，启动和放大伤口愈合早期的局部炎症。IL-1β 和 IL-23 抑制 DETCs 产生 IGF-1，从而阻碍伤口愈合。Vγ4 T 细胞、表皮细胞和 DETCs 之间可能存在一个功能环，以调节伤口修复。
