皮肤伤口愈合过程中的瘙痒产生机制

细胞因子TGF-β诱导真皮树突状细胞表达白介素31，从而激活感觉神经元并刺激伤口瘙痒。皮肤伤口愈合与瘙痒的不适感有关。研究人员揭示了这种瘙痒的潜在机制，并集中在愈合过程中释放的可溶性因子。研究人员在瘙痒反应高峰期的皮肤伤口组织中发现大量白细胞介素31（IL-31）。 Il31-/-小鼠缺乏伤口诱导的瘙痒反应。IL-31由招募到伤口的皮肤传统2型树突状细胞（cDC2）释放，并增加了瘙痒感觉神经元的敏感性。

 从晚期伤口分离的cDC2转移到健康皮肤中足以诱导瘙痒，且依赖于IL-31表达。在体外向皮肤DC中添加促进伤口愈合的细胞因子TGF-β1足以诱导Il31表达，并且Tgfbr1f/f CD11c-Cre小鼠在体内伤口中显示出抓挠的减少以及Il31表达的降低。

 因此，cDC2在伤口愈合期间通过TGF-β-IL-31轴促进皮肤瘙痒，这可能对于伤口瘙痒有治疗意义。

附：英文原文

Title: The Cytokine TGF-β Induces Interleukin-31 Expression from Dermal Dendritic Cells to Activate Sensory Neurons and Stimulate Wound Itching

Author: Junji Xu, Peter Zanvit, Lei Hu, Pang-Yen Tseng, Na Liu, Fu Wang, Ousheng Liu, Dunfang Zhang, Wenwen Jin, Nancy Guo, Yichen Han, Jessica Yin, Alexander Cain, Mark A. Hoon, Songlin Wang, WanJun Chen

Issue&Volume: 2020-07-15

Abstract: 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 Tgfbr1f/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.

DOI: 10.1016/j.immuni.2020.06.023

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30278-8