Senescent fibroblast facilitates re-epithelization and collagen deposition in radiation-induced skin injury through IL-33-mediated macrophage polarization

被引：4

作者：

Chen, Yan ^{[1
]}

Ma, Le ^{[1
]}

Cheng, Zhuo ^{[1
]}

Hu, Zhihe ^{[1
]}

Xu, Yang ^{[1
]}

Wu, Jie ^{[1
]}

Dai, Yali ^{[1
]}

Shi, Chunmeng ^{[1
]}

机构：

[1] Third Mil Med Univ, Army Med Univ, Inst Rocket Force Med, State Key Lab Trauma & Chem Poisoning, Chongqing 400038, Peoples R China

来源：

JOURNAL OF TRANSLATIONAL MEDICINE | 2024年 / 22卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Senescence; IL-33; Macrophages; Radiation-induced skin injury; IN-VIVO; IMPROVES; TISSUE; IL-33; MICE; MOUSE; CELLS;

D O I：

10.1186/s12967-024-04972-8

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

BackgroundThe need for radiotherapy among the elderly rises with increasing life expectancy and a corresponding increase of elderly cancer patients. Radiation-induced skin injury is one of the most frequent adverse effects in radiotherapy patients, severely limiting their life quality. Re-epithelialization and collagen deposition have essential roles in the recovery of skin injuries induced by high doses of ionizing radiation. At the same time, radiation-induced senescent cells accumulate in irradiated tissues. However, the effects and mechanisms of senescent cells on re-epithelialization and collagen deposition in radiation-induced skin injury have not been fully elucidated.ResultsHere, we identified a role for a population of senescent cells expressing p16 in promoting re-epithelialization and collagen deposition in radiation-induced skin injury. Targeted ablation of p16+ senescent cells or treatment with Senolytics resulted in the disruption of collagen structure and the retardation of epidermal coverage. By analyzing a publicly available single-cell sequencing dataset, we identified fibroblasts as a major contributor to the promotion of re-epithelialization and collagen deposition in senescent cells. Notably, our analysis of publicly available transcriptome sequencing data highlighted IL-33 as a key senescence-associated secretory phenotype produced by senescent fibroblasts. Neutralizing IL-33 significantly impedes the healing process. Finally, we found that the effect of IL-33 was partly due to the modulation of macrophage polarization.ConclusionsIn conclusion, our data suggested that senescent fibroblasts accumulated in radiation-induced skin injury sites participated in wound healing mainly by secreting IL-33. This secretion regulated the local immune microenvironment and macrophage polarization, thus emphasizing the importance of precise regulation of senescent cells in a phased manner.

引用

页数：21