Role of MR1-driven signals and amphiregulin on the recruitment and repair function of MAIT cells during skin wound healing.
Role of MR1-driven signals and amphiregulin on the recruitment and repair function of MAIT cells during skin wound healing.
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MR1 驱动信号和双调蛋白对皮肤伤口愈合过程中 MAIT 细胞招募和修复功能的作用。
DOI：
10.1016/j.immuni.2022.12.004
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发表时间：
2023-01-10
期刊：
影响因子：
32.4
通讯作者：
Salou, Marion
中科院分区：
文献类型：
--
作者：
du Halgouet, Anastasia;Darbois, Aurelie;Alkobtawi, Mansour;Mestdagh, Martin;Alphonse, Aurelia;Premel, Virginie;Yvorra, Thomas;Colombeau, Ludovic;Rodriguez, Raphael;Zaiss, Dietmar;El Morr, Yara;Bugaut, Helene;Legoux, Francois;Perrin, Laetitia;Aractingi, Selim;Golub, Rachel;Lantz, Olivier;Salou, Marion
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。除了抗菌特性之外，粘膜相关不变T（MAIT）细胞表达组织修复转录组学程序，并且在扩增时促进皮肤伤口愈合。在此，我们使用一个类人小鼠模型的全层皮肤切除，以评估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细胞已经表达了稳定状态下的修复程序。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、联体共生和过继转移实验，我们发现MAIT细胞以T细胞受体（TCR）非依赖性但CXCR 6趋化因子受体依赖性的方式迁移到伤口中。切除后MAIT细胞分泌的双调蛋白促进伤口愈合。修复功能的表达可能不依赖于持续的TCR刺激。总的来说，我们的研究为MAIT细胞在皮肤中的伤口愈合功能提供了机制上的见解。MAIT细胞加速类人皮肤损伤模型中的伤口闭合MAIT细胞通过CXCR 6/CXCL 16迁移到发炎的皮肤中，并且独立于MR 1，MAIT细胞促修复功能独立于持续的TCR信号传导，MAIT细胞产生的双调蛋白加速伤口闭合MAIT细胞具有组织修复特性，但潜在的机制尚不清楚。du Halgouet et et al.证明MAIT细胞通过增加上皮增殖加速伤口闭合。MAIT细胞以CXCL 16/CXCR 6依赖性MR 1非依赖性方式被招募到受损皮肤中，并且它们的促修复作用与双调蛋白的产生有关。
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. MAIT cells accelerate wound closure in a human-like skin injury model MAIT cells migrate into the inflamed skin via CXCR6/CXCL16 and independently of MR1 MAIT cell pro-repair function is independent of sustained TCR signaling Amphiregulin production by MAIT cells accelerates wound closure MAIT cells have tissue repair properties, but the underlying mechanisms are unclear. du Halgouet et al. demonstrate that MAIT cells accelerate wound closure by increasing epithelial proliferation. MAIT cells are recruited into the injured skin in a CXCL16/CXCR6-dependent MR1-independent manner, and their pro-repair effect is related to amphiregulin production.
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影响因子：
6.5
作者：
Kennedy-Crispin, Milene;Billick, Erika;Mitsui, Hiroshi;Gulati, Nicholas;Fujita, Hideki;Gilleaudeau, Patricia;Sullivan-Whalen, Mary;Johnson-Huang, Leanne M.;Suarez-Farinas, Mayte;Krueger, James G.
通讯作者：
Krueger, James G.
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
15.9
作者：
Cui, Yue;Franciszkiewicz, Katarzyna;Lantz, Olivier
通讯作者：
Lantz, Olivier
DOI：
10.1126/science.aax6624
发表时间：
2019-10-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Constantinides MG;Link VM;Tamoutounour S;Wong AC;Perez-Chaparro PJ;Han SJ;Chen YE;Li K;Farhat S;Weckel A;Krishnamurthy SR;Vujkovic-Cvijin I;Linehan JL;Bouladoux N;Merrill ED;Roy S;Cua DJ;Adams EJ;Bhandoola A;Scharschmidt TC;Aubé J;Fischbach MA;Belkaid Y
通讯作者：
Belkaid Y
影响因子：
4.8
作者：
Brinkmann, V;Davis, MD;Lynch, KR
通讯作者：
Lynch, KR