CD4⁺LAG3⁺T cells are decreased in SSc-ILD and affect fibroblast mesenchymal transition by TGF-β3

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.