法国居里研究所Marion Salou和Olivier Lantz共同合作,近期取得重要工作进展。他们研究发现MR1驱动信号和双调节蛋白在皮肤创伤愈合过程中对MAIT细胞募集和修复功能的作用。
据介绍,组织修复过程在机械或感染相关损伤后维持适当的器官功能。除了抗菌特性外,粘膜相关不变T(MAIT)细胞表达组织修复转录组程序,并在扩张时促进皮肤伤口愈合。
研究人员使用类人小鼠全厚度皮肤切除模型来评估MAIT细胞组织修复功能的潜在机制。单细胞RNA测序分析表明,皮肤MAIT细胞已经在稳定状态下表达了修复程序。皮肤切除后,MAIT细胞促进角质形成细胞增殖,从而加速愈合。通过皮肤移植、异种共生和过继转移实验,研究人员发现MAIT细胞以T细胞受体(TCR)不依赖但CXCR6趋化因子受体依赖的方式迁移到伤口部位。切除后MAIT细胞分泌的双调节蛋白促进伤口愈合。修复功能的表达可能与持续的TCR刺激无关。
总之,这一研究为皮肤中MAIT细胞在伤口愈合功能方面提供了机制上的见解。
附:英文原文
Title: Role of MR1-driven signals and amphiregulin on the recruitment and repair function of MAIT cells during skin wound healing
Author: Anastasia du Halgouet, Aurélie Darbois, Mansour Alkobtawi, Martin Mestdagh, Aurélia Alphonse, Virginie Premel, Thomas Yvorra, Ludovic Colombeau, Raphal Rodriguez, Dietmar Zaiss, Yara El Morr, Hélène Bugaut, Franois Legoux, Laetitia Perrin, Selim Aractingi, Rachel Golub, Olivier Lantz, Marion Salou
Issue&Volume: 2023/01/10
Abstract: Tissue repair processes maintain proper organ function following mechanical or infection-related damage. In addition to antibacterial properties, mucosal associated invariant T (MAIT) cells express a tissue repair transcriptomic program and promote skin wound healing when expanded. Herein, we use a human-like mouse model of full-thickness skin excision to assess the underlying mechanisms of MAIT cell tissue repair function. Single-cell RNA sequencing analysis suggested that skin MAIT cells already express a repair program at steady state. Following skin excision, MAIT cells promoted keratinocyte proliferation, thereby accelerating healing. Using skin grafts, parabiosis, and adoptive transfer experiments, we show that MAIT cells migrated into the wound in a T cell receptor (TCR)-independent but CXCR6 chemokine receptor-dependent manner. Amphiregulin secreted by MAIT cells following excision promoted wound healing. Expression of the repair function was probably independent of sustained TCR stimulation. Overall, our study provides mechanistic insights into MAIT cell wound healing function in the skin.
DOI: 10.1016/j.immuni.2022.12.004
Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00640-9
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