IFN‐γ<sup>+</sup>IL‐17<sup>+</sup>Th17 cells regulate fibrosis through secreting IL‐21 in systemic scleroderma
Xiaojing Xing, Anqi Li, Hong Yien Tan, Yong Zhou
Abstract
Abstract This study aimed to explore the function of IFN‐γ + IL‐17 + Th17 cells on fibrosis in systemic scleroderma (SSc). Blood and skin samples were collected from 20 SSc cases and 10 healthy individuals. The percentage of IFN‐γ + IL‐17 + Th17 cells was detected using flow cytometry. The in vitro induction of IFN‐γ + IL‐17 + Th17 cells was performed adopting PHA and rIL‐12. Gene expression was detected via quantitative real‐time polymerase chain reaction (qRT‐PCR), whereas western blot analysis was adopted for protein analysis. The distribution of IFN‐γ + IL‐17 + Th17 cells was significantly increased in SSc cases and positively correlated with SSc stages ( P = .031), disease duration ( P = .016), activity ( P = .025) and skin scores ( P < .001). In vitro, IFN‐γ + IL‐17 + Th17 cells could promote the expressions of α‐SMA and COL1A1, revealing increased fibroblasts’ proliferation and enhanced collagen‐secreting capacity. In addition, IL‐21 expression was significantly increased in co‐culture medium of IFN‐γ + IL‐17 + Th17 cells and fibroblasts ( P < .001). IL‐21 neutralizer treatment resulted in the down‐regulation of α‐SMA and COL1A1. IL‐21 was confirmed as an effector of IFN‐γ + IL‐17 + Th17 cells in fibrosis process. The distribution of IFN‐γ + IL‐17 + Th17 cells was significantly increased in SSc cases and positively correlated with disease activity. IFN‐γ + IL‐17 + Th17 cells could promote fibroblast proliferation and enhance collagen‐secreting ability via producing IL‐21, thus contributing to fibrosis in SSc.