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The effects of interleukin-35 and interleukin-10 on pulmonary inflammation and fibrosis in a bleomycin-induced systemic sclerosis mouse model
Y. Huang1, W. Zeng2, X. Liao3, F. Qin4, X. Ma5, J. Pan6, G. Li7, K. Tang8, L. Lei9
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province; and Department of Rheumatology and Immunology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi Province, China.
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China.
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China.
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China.
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China.
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China.
- Department of Rheumatology and Immunology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi Province, China.
- Department of Rheumatology and Immunology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi Province, China.
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China. leiling1972@aliyun.com
CER18006
2025 Vol.43, N°8
PI 1398, PF 1407
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PMID: 40153333 [PubMed]
Received: 22/07/2024
Accepted : 18/11/2024
In Press: 19/03/2025
Published: 01/08/2025
Abstract
OBJECTIVES:
We investigated the impact of IL-35 and IL-10 on the immune response and pulmonary fibrosis using a bleomycin (BLM)-induced SSc mouse model.
METHODS:
BLM was administered subcutaneously to Balb/c mice and either mouse recombinant (rm)IL-35, rmIL-10 or neutralising antibody of IL-35 and IL-10 was injected intraperitoneally after BLM administration. Lung fibrosis was assessed by the pathological alterations, hydroxyproline content, and the collagen I and α-SMA mRNA expression. The expression of immune cells and their related factors were respectively measured by flow cytometry and ELISA. Western blot was used to measure STAT3 pathway expression.
RESULTS:
Compared with controls, BLM exposure induced increased Ashcroft ratings, hydroxyproline and lung collagen I and α-SMA expression, which was lessened by rmIL-35 or rmIL-10 intervention, while it did not change after blocking IL-35 and IL-10. BLM exposure increased IL-4 and IL-17A expression in bronchoalveolar lavage (BAL) supernatant, which was downregulated by rmIL-35 or rmIL-10 administration. Compared with the BLM group, the RmIL-35 and rmIL-10 group both downregulated Th2/nTreg and Th17/nTreg percentage, while increased Treg cell proportion in the spleen. Moreover, the spleen iTr35 cell ratio was negatively correlated with BAL supernatant IL-17A and IL-4 levels and lung collagen I and α-SMA expression. Further pathway analysis revealed that rmIL-35 administration decreased the phosphorylation of STAT3 compared with the BLM group.
CONCLUSIONS:
Our findings suggest that IL-35 and IL-10 might alleviate pulmonary inflammation and fibrosis via upregulating the proportion of Treg cells and reducing BAL supernatant IL-17A and IL-4 levels in a bleomycin-induced SSc mouse model.
