美国加州大学旧金山分校Michael D. Rosenblum研究组近日取得一项新成果。他们发现早期炎症引发了皮肤中的2 型辅助性 T (TH2)细胞-成纤维细胞壁龛。相关论文于2021年10月27日发表在《自然》杂志上。
他们发现由新生儿调节性 T 细胞的短暂减少引起的时限性新生儿炎症会导致小鼠皮肤皮下组织的失调。这伴随着TH2细胞在独特的微解剖壁龛内的选择性积累。 TH2 细胞通过与皮肤筋膜中的成纤维细胞群相互作用而维持到成年期，他们称之为 TH2 相互作用的筋膜成纤维细胞 (TIFF)，它们响应 TH2 细胞因子而扩增以形成皮下纤维带。由于新生儿炎症引起的 TH2-TIFF 壁龛的激活使皮肤对伤口的修复反应发生改变。
此外，他们在健康人类皮肤中鉴定出表达 TIFF 转录特征的成纤维细胞，并在嗜酸性筋膜炎（一种以皮肤筋膜炎症和纤维化为特征的孤儿疾病）中检测到这些细胞的水平很高。综上所述，这些数据定义了皮肤中先前未鉴定的 TH2 细胞壁龛，并在功能上表征了与疾病相关的成纤维细胞群。结果还表明了一种免疫启动机制，即生命早期的炎症在适应性免疫细胞和基质细胞之间建立网络，以在组织中建立一个终生维持的免疫设定点。
据悉，生命早期的炎症可以引发外周组织的局部免疫环境，这会导致免疫基调的持久变化，从而赋予疾病保护或易感性。促使许多非淋巴组织中免疫基调发生变化的细胞和分子机制在很大程度上仍然未知。
附：英文原文
Title: Early-life inflammation primes a T helper 2 cell–fibroblast niche in skin
Author: Boothby, Ian C., Kinet, Maxime J., Boda, Devi P., Kwan, Elaine Y., Clancy, Sean, Cohen, Jarish N., Habrylo, Ireneusz, Lowe, Margaret M., Pauli, Mariela, Yates, Ashley E., Chan, Jamie D., Harris, Hobart W., Neuhaus, Isaac M., McCalmont, Timothy H., Molofsky, Ari B., Rosenblum, Michael D.
Issue&Volume: 2021-10-27
Abstract: Inflammation early in life can prime the local immune milieu of peripheral tissues, which can cause lasting changes in immunological tone that confer disease protection or susceptibility1. The cellular and molecular mechanisms that prompt changes in immune tone in many nonlymphoid tissues remain largely unknown. Here we find that time-limited neonatal inflammation induced by a transient reduction in neonatal regulatory T cells causes a dysregulation of subcutaneous tissue in mouse skin. This is accompanied by the selective accumulation of type 2 helper T (TH2) cells within a distinct microanatomical niche. TH2 cells are maintained into adulthood through interactions with a fibroblast population in skin fascia that we refer to as TH2-interacting fascial fibroblasts (TIFFs), which expand in response to TH2 cytokines to form subcutaneous fibrous bands. Activation of the TH2–TIFF niche due to neonatal inflammation primes the skin for altered reparative responses to wounding. Furthermore, we identify fibroblasts in healthy human skin that express the TIFF transcriptional signature and detect these cells at high levels in eosinophilic fasciitis, an orphan disease characterized by inflammation and fibrosis of the skin fascia. Taken together, these data define a previously unidentified TH2 cell niche in skin and functionally characterize a disease-associated fibroblast population. The results also suggest a mechanism of immunological priming whereby inflammation early in life creates networks between adaptive immune cells and stromal cells to establish an immunological set-point in tissues that is maintained throughout life.
DOI: 10.1038/s41586-021-04044-7
Source: https://www.nature.com/articles/s41586-021-04044-7
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
