2. Academic Validation
  3. IL-22 inhibits bleomycin-induced pulmonary fibrosis in association with inhibition of IL-17A in mice

IL-22 inhibits bleomycin-induced pulmonary fibrosis in association with inhibition of IL-17A in mice

  • Arthritis Res Ther. 2022 Dec 24;24(1):280. doi: 10.1186/s13075-022-02977-6.
Ziye Qu 1 2,  Wencan Dou 1 2,  Kexin Zhang 3,  Lili Duan 4,  Dongmei Zhou 5 6,  Songlou Yin 7 8
Affiliations

Affiliations

  • 1 Department of Rheumatology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, China.
  • 2 The First Clinical Medicine School, Xuzhou Medical University, Xuzhou, 221002, China.
  • 3 Blood Diseases Institute, Xuzhou Medical University, Xuzhou, 221002, China.
  • 4 Department of Rheumatology, The People's Hospital of Jiawang District of Xuzhou, Xuzhou, 221011, China.
  • 5 Department of Rheumatology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, China. [email protected].
  • 6 The First Clinical Medicine School, Xuzhou Medical University, Xuzhou, 221002, China. [email protected].
  • 7 Department of Rheumatology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, China. [email protected].
  • 8 The First Clinical Medicine School, Xuzhou Medical University, Xuzhou, 221002, China. [email protected].
PMID: 36564791 DOI: 10.1186/s13075-022-02977-6
Abstract

Background: Interstitial lung disease, a common extra-articular complication of connective tissue disease, is characterized by progressive and irreversible pulmonary inflammation and fibrosis, which causes significant mortality. IL-22 shows a potential in regulating chronic inflammation and possibly plays an anti-fibrotic role by protecting epithelial cells. However, the detailed effects and underlying mechanisms are still unclear. In this study, we explored the impact of IL-22 on pulmonary fibrosis both in vivo and in vitro.

Methods: To induce pulmonary fibrosis, wild-type mice and IL-22 knockout mice were intratracheally injected with bleomycin followed by treatments with recombinant IL-22 or IL-17A neutralizing antibody. We investigated the role of IL-22 on bleomycin-induced pulmonary fibrosis and the mechanism in the possible interaction between IL-22 and IL-17A. Fibrosis-related genes were detected using RT-qPCR, western blot, and immunofluorescence. Inflammatory and fibrotic changes were assessed based on histological features. We also used A549 human alveolar epithelial cells, NIH/3T3 mouse fibroblast cells, and primary mouse lung fibroblasts to study the impact of IL-22 on fibrosis in vitro.

Results: IL-22 knockout mice showed aggravated pulmonary fibrosis compared with wild-type mice, and injection of recombinant IL-22 decreased the severe fibrotic manifestations in IL-22 knockout mice. In Cell Culture assays, IL-22 decreased protein levels of Collagen I in A549 cells, NIH/3T3 cells, and primary mouse lung fibroblasts. IL-22 also reduced the protein level of Collagen I in NIH/3T3 cells which were co-cultured with T cells. Mechanistically, IL-22 reduced the Th17 cell proportion and IL-17A mRNA level in lung tissues, and treatment with an IL-17A neutralizing antibody alleviated the severe pulmonary fibrosis in IL-22 knockout mice. The IL-17A neutralizing antibody also reduced Collagen I expression in NIH/3T3 cells in vitro. Knockdown of IL-17A with siRNAs or administration of IL-22 in NIH/3T3 cells and MLFs decreased expression of Collagen I, an effect blocked by concurrent use of recombinant IL-17A.

Conclusions: IL-22 mediated an anti-fibrogenesis effect in the bleomycin-induced pulmonary fibrosis model and this effect was associated with inhibition of IL-17A.

Keywords

Bleomycin; IL-17A; IL-22; Pulmonary fibrosis.

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