CD4+LAG3+T cells are decreased in SSc-ILD and affect fibroblast mesenchymal transition by TGF-β3
Linmang Qin, Haobo Lin, Fu Zhu, Jieying Wang, Tianxiao Feng, Ting Xu, Guangfeng Zhang, Xiao Zhang
Abstract
Pulmonary fibrosis frequently occurs in rheumatic conditions, particularly systemic sclerosis-associated interstitial lung disease (SSc-ILD). The pathology involves cell transformation into interstitial structures and collagen accumulation. CD4 + LAG3 + T cells, known for immune inhibition, are relevant in autoimmunity. This study investigates CD4 + LAG3 + T cells in SSc-ILD. Clinical analysis revealed a correlation between CD4 + LAG3 + T cells and interleukin-6 (IL-6) and erythrocyte sedimentation rate (ESR). Using primary human lung fibroblasts (pHLFs) and murine bone marrow-derived macrophages (BMDMs), we showed that CD4 + LAG3 + T cells secreted TGF-β3 inhibits TGF-β1-induced mesenchymal transformation, modulates cellular function, and reduces collagen release. In mouse models, CD4 + LAG3 + T cells exhibited potential in alleviating bleomycin-induced pulmonary fibrosis. This study emphasizes CD4 + LAG3 + T cells' therapeutic promise against fibrosis and proposes their role as biomarkers.