Tff1-expressing Tregs in lung prevent exacerbation of Bleomycin-induced pulmonary fibrosis

Front Immunol. 2024 Sep 2:15:1440918. doi: 10.3389/fimmu.2024.1440918. eCollection 2024.

Abstract

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 expressing 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 did not change the pathological condition, 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.

Keywords: Bleomycin; Tff1; Treg; VeDTR; fibrosis.

MeSH terms

  • Animals
  • Bleomycin* / adverse effects
  • Disease Models, Animal
  • Interleukin-33 / genetics
  • Interleukin-33 / metabolism
  • Lung* / immunology
  • Lung* / metabolism
  • Lung* / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pulmonary Fibrosis* / chemically induced
  • Pulmonary Fibrosis* / metabolism
  • T-Lymphocytes, Regulatory* / immunology
  • T-Lymphocytes, Regulatory* / metabolism
  • Trefoil Factor-1* / genetics
  • Trefoil Factor-1* / metabolism

Substances

  • Bleomycin
  • Trefoil Factor-1
  • Interleukin-33