Cutaneous wound healing is associated with the unpleasant sensation of itching. Here we investigated the mechanisms underlying this type of itch, focusing on the contribution of soluble factors released during healing. We found high amounts of interleukin 31 (IL-31) in skin wound tissue during the peak of itch responses. Il31^−/− mice lacked wound-induced itch responses. IL-31 was released by dermal conventional type 2 dendritic cells (cDC2s) recruited to wounds and increased itch sensory neuron sensitivity. Transfer of cDC2s isolated from late-stage wounds into healthy skin was sufficient to induce itching in a manner dependent on IL-31 expression. Addition of the cytokine TGF-β1, which promotes wound healing, to dermal DCs in vitro was sufficient to induce Il31 expression, and Tgfbr1^f/f CD11c-Cre mice exhibited reduced scratching and decreased Il31 expression in wounds in vivo. Thus, cDC2s promote itching during skin would healing via a TGF-β-IL-31 axis with implications for treatment of wound itching.

皮肤伤口愈合与瘙痒的不适感有关。在这里，我们研究了这种瘙痒的潜在机制，重点是在愈合过程中释放的可溶性因子的贡献。我们在瘙痒反应高峰期的皮肤伤口组织中发现了大量的白介素31（IL-31）。Il31 ^-/-小鼠缺乏伤口诱导的瘙痒反应。IL-31由募集到伤口的皮肤常规2型树突状细胞（cDC2s）释放，并增加了瘙痒感觉神经元敏感性。从晚期伤口分离的cDC2转移至健康皮肤足以以依赖IL-31表达的方式诱导瘙痒。在体外向皮肤DC添加促进伤口愈合的细胞因子TGF-β1足以诱导Il31表达和Tgfbr1 ^{f / f} CD11c-Cre小鼠在体内伤口中显示出减少的抓挠和Il31表达的降低。因此，cDC2s促进皮肤瘙痒，将通过TGF-β-IL-31轴愈合，从而有助于治疗伤口瘙痒。