加拿大卡尔加里大学Jeff Biernaskie课题组发现，成纤维细胞的炎症启动决定驯鹿皮肤的再生与纤维性修复。2022年12月8日出版的《细胞》杂志发表了这项成果。

研究人员报告说，驯鹿鹿茸皮肤（velvet）的全厚度损伤会再生，而背部皮肤会形成纤维化的疤痕。单细胞多组学研究显示，未受伤的鹿茸成纤维细胞类似于人类的胎儿成纤维细胞，而背部皮肤成纤维细胞表达的炎症介质模仿了人类和啮齿类成纤维细胞的促纤维化。因此，损伤引起了特定部位的免疫反应：背部皮肤成纤维细胞在修复过程中扩大了髓系细胞的浸润和成熟，而velvet成纤维细胞则采用免疫抑制表型，限制白细胞的招募并加速免疫解决。

将velvet异位移植到形成疤痕的背部皮肤最初是再生的，但逐渐过渡到纤维化表型，类似于人类报道的无疤痕胎儿到疤痕形成的过渡。皮肤再生通过加强或通过中和这些病理性的纤维细胞-免疫相互作用而减弱或加强。驯鹿代表了一个强大的比较模型，可用于研究人员不同的伤口愈合结果。这些结果提示成纤维细胞-免疫相互作用的脱钩是减轻疤痕的一个有望方法。

据悉，成年哺乳动物的皮肤伤口通过形成纤维化的疤痕而愈合。

附：英文原文

Title: Fibroblast inflammatory priming determines regenerative versus fibrotic skin repair in reindeer

Author: Sarthak Sinha, Holly D. Sparks, Elodie Labit, Hayley N. Robbins, Kevin Gowing, Arzina Jaffer, Eren Kutluberk, Rohit Arora, Micha Sam Brickman Raredon, Leslie Cao, Scott Swanson, Peng Jiang, Olivia Hee, Hannah Pope, Matt Workentine, Kiran Todkar, Nilesh Sharma, Shyla Bharadia, Keerthana Chockalingam, Luiz G.N. de Almeida, Mike Adam, Laura Niklason, S. Steven Potter, Ashley W. Seifert, Antoine Dufour, Vincent Gabriel, Nicole L. Rosin, Ron Stewart, Greg Muench, Robert McCorkell, John Matyas, Jeff Biernaskie

Issue&Volume: 2022/12/08

Abstract: Adult mammalian skin wounds heal by forming fibrotic scars. We report that full-thickness injuries of reindeer antler skin (velvet) regenerate, whereas back skin forms fibrotic scar. Single-cell multi-omics reveal that uninjured velvet fibroblasts resemble human fetal fibroblasts, whereas back skin fibroblasts express inflammatory mediators mimicking pro-fibrotic adult human and rodent fibroblasts. Consequently, injury elicits site-specific immune responses: back skin fibroblasts amplify myeloid infiltration and maturation during repair, whereas velvet fibroblasts adopt an immunosuppressive phenotype that restricts leukocyte recruitment and hastens immune resolution. Ectopic transplantation of velvet to scar-forming back skin is initially regenerative, but progressively transitions to a fibrotic phenotype akin to the scarless fetal-to-scar-forming transition reported in humans. Skin regeneration is diminished by intensifying, or enhanced by neutralizing, these pathologic fibroblast-immune interactions. Reindeer represent a powerful comparative model for interrogating divergent wound healing outcomes, and our results nominate decoupling of fibroblast-immune interactions as a promising approach to mitigate scar.

DOI: 10.1016/j.cell.2022.11.004

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)01414-3