Regulatory T (Treg) cells, expressing CD25 (interleukin-2 receptor α chain) and Foxp3 transcription factor, maintain immunological self-tolerance and suppress various immune responses. Here we report a feature of skin Treg cells expanded by ultraviolet B (UVB) exposure. We found that skin Treg cells possessing a healing function are expanded by UVB exposure with the expression of an endogenous opioid precursor, proenkephalin (PENK). Upon UVB exposure, skin Treg cells were expanded with a unique TCR repertoire. Also, they highly expressed a distinctive set of genes enriched in “wound healing involved in inflammatory responses” and the “neuropeptide signaling pathway,” as indicated by the high expression of Penk. We found that not only was PENK expression at the protein level detected in the UVB-expanded skin Treg (UVB-skin Treg) cells, but that a PENK-derived neuropeptide, methionine enkephalin (Met-ENK), from Treg cells promoted the outgrowth of epidermal keratinocytes in an ex vivo skin explant assay. Notably, UVB-skin Treg cells also promoted wound healing in an in vivo wound closure assay. In addition, UVB-skin Treg cells produced amphiregulin (AREG), which plays a key role in Treg-mediated tissue repair. Identification of a unique function of PENK⁺ UVB-skin Treg cells provides a mechanism for maintaining skin homeostasis.

表达CD25（白介素2受体α链）和Foxp3转录因子的调节性T（Treg）细胞保持免疫学自耐受性并抑制各种免疫反应。在这里，我们报告通过紫外线B（UVB）暴露而扩展的皮肤Treg细胞的功能。我们发现具有内源性阿片类前体前脑啡肽（PENK）的表达的UVB暴露可扩大具有愈合功能的皮肤Treg细胞。暴露于UVB后，皮肤Treg细胞具有独特的TCR成分。此外，他们还表达了一组独特的基因，这些基因富含“涉及炎症反应的伤口愈合”和“神经肽信号传导途径”，如Penk的高表达所表明。我们发现，不仅在UVB扩展的皮肤Treg（UVB-皮肤Treg）细胞中检测到了蛋白水平的PENK表达，而且来自Treg细胞的PENK衍生的神经肽蛋氨酸脑啡肽（Met-ENK）促进了这种产物的生长。在离体皮肤外植体测定中测定表皮角质形成细胞。值得注意的是，在体内伤口闭合试验中，UVB皮肤Treg细胞还促进了伤口愈合。此外，UVB皮肤Treg细胞产生了两性调节蛋白（AREG），其在Treg介导的组织修复中起关键作用。PENK ⁺ UVB-皮肤Treg细胞独特功能的鉴定提供了维持皮肤稳态的机制。