The lymphocyte-specific protein tyrosine kinase-specific inhibitor A-770041 attenuates lung fibrosis via the suppression of TGF-β production in regulatory T-cells
Fig 4
A-770041 and nintedanib inhibit the production of TGF-β in regulatory T-cells.
Tregs and TGF-β1-producing Tregs infiltrating BLM-treated lung tissues were examined by flow cytometry. Tregs were identified as CD3e+ CD4+ Foxp3+ TGF-β1+ cells, and the gating strategy for the identification of TGF-β1-producing Tregs is shown (A). Mice received a single transbronchial instillation of 3.0 mg/kg BLM on Day 0, and lungs were collected on days 0, 7, 14, and 21. Time courses of the percentages of whole Treg cells to CD4+ T-cells (B) and that of TGF-β1+ Tregs to Tregs (C) were evaluated (Day 0, n = 4; Day 7, n = 8; Day 14, n = 8; Day 21, n = 6). After BLM treatment, A-770041 (5 mg/kg/day), nintedanib (60 mg/kg/day), or vehicle was administered daily, and lungs were collected on day 7 (n = 5). The percentages of whole Tregs to CD4+ T-cells (D) and that of TGF-β1+ Tregs to Tregs (E) were evaluated by flow cytometry. *p<0.05 versus Day 0 samples; **p<0.05 versus group treated with BLM without A-770041 or nintedanib.