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
Affiliations
Linmang Qin
Department of Rheumatology and Immunology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China
Haobo Lin
Department of Rheumatology and Immunology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China
Fu Zhu
Liuzhou Worker’s Hospital, Liuzhou 545007, China
Jieying Wang
Department of Rheumatology and Immunology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China
Tianxiao Feng
Department of Rheumatology and Immunology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China
Ting Xu
Department of Rheumatology and Immunology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China
Guangfeng Zhang
Department of Rheumatology and Immunology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China
Xiao Zhang
Department of Rheumatology and Immunology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China; Corresponding author
Summary: 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.
