Tff1-expressing Tregs in lung prevents exacerbation of Bleomycin-induced pulmonary fibrosis (RNA-Seq)

Bleomycin (BLM) induces lung injury, leading to inflammation and pulmonary fibrosis. Regulatory T cells (Tregs) maintain self-tolerance and control host immune responses. However, little is known about their involvement in the pathology of pulmonary fibrosis. Here we show that a unique Treg subset that expresses trefoil factor family 1(Tff1) emerges in the BLM-injured lung. These Tff1-expressing Tregs (Tff1-Tregs) were induced by IL-33. Moreover, although Tff1 ablation in Tregs had no impact, selective ablation of Tff1-Tregs using an intersectional genetic method promoted pro-inflammatory features of macrophages in the injured lung and exacerbated the fibrosis. Taken together, our study revealed the presence of a unique Treg subset expressing Tff1 in BLM-injured lungs and their critical role in the injured lung to ameliorate fibrosis. Overall design: GFP+CD4+ T cells were sorted from lung and spleen of BLM-administrated FDG-mice at day 15.

博来霉素（Bleomycin, BLM）可诱导肺损伤，进而引发炎症反应与肺纤维化。调节性T细胞（Regulatory T cells, Tregs）能够维持机体自身耐受并调控宿主免疫应答，但目前对于其在肺纤维化病理过程中的参与作用尚不清楚。本研究发现，在博来霉素损伤的肺组织中，会出现一类表达三叶因子家族1（trefoil factor family 1, Tff1）的独特Treg亚群。这类表达Tff1的Tregs（Tff1-Tregs）可由白介素33（Interleukin-33, IL-33）诱导产生。此外，尽管直接敲除Tregs中的Tff1并未产生显著影响，但利用交叉遗传技术选择性清除Tff1-Tregs后，会促进损伤肺内巨噬细胞的促炎表型，并加重肺纤维化程度。综上，本研究揭示了博来霉素损伤肺中存在一类表达Tff1的独特Treg亚群，并阐明了其在损伤肺内缓解纤维化进程中的关键作用。整体实验设计：于博来霉素给药后第15天，从经博来霉素处理的FDG小鼠的肺与脾脏中分选绿色荧光蛋白（Green Fluorescent Protein, GFP）阳性CD4阳性T细胞。