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

iScience (Dec 2023)

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

Journal volume & issue: Vol. 26, no. 12
p. 108225

Abstract

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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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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