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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


1, 2, 3, 4, 5, 6, 7, 8, 9

 

  1. 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.
  2. Department of Rheumatology and Immunology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China.
  3. Department of Rheumatology and Immunology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China.
  4. Department of Rheumatology and Immunology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China.
  5. Department of Rheumatology and Immunology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China.
  6. Department of Rheumatology and Immunology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China.
  7. Department of Rheumatology and Immunology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi Province, China.
  8. Department of Rheumatology and Immunology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi Province, China.
  9. Department of Rheumatology and Immunology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China. leiling1972@aliyun.com

CER18006
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PMID: 40153333 [PubMed]

Received: 22/07/2024
Accepted : 18/11/2024
In Press: 19/03/2025

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 BLM group, 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 cells 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 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.

DOI: https://doi.org/10.55563/clinexprheumatol/1t3s0i

Rheumatology Article

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