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  • Title: In vivo anti-inflammatory activities of novel cytokine IL-38 in Murphy Roths Large (MRL)/lpr mice.
    Author: Chu M, Tam LS, Zhu J, Jiao D, Liu H, Cai Z, Dong J, Kai Lam CW, Wong CK.
    Journal: Immunobiology; 2017 Mar; 222(3):483-493. PubMed ID: 27769564.
    Abstract:
    The newly named interleukin (IL)-36 subfamily member IL-38 has been shown to exert anti-inflammatory activity. However, the in vivo immunomodulatory activity of IL-38 was poorly investigated in systemic lupus erythematosus (SLE). We have investigated the expression of CD4+IL-17+ Th17, CD4+IFN-γ+ Th1 and CD3+CD4-CD8- double negative (DN) T cells and the related immunopathological mechanisms in female MRL/lpr mice model of spontaneous lupus-like disease, with or without IL-38 treatment. Intravenous administration of murine recombinant IL-38 into MRL/lpr mice can ameliorate the lupus-like clinical symptoms including proteinuria, leukocyteuria and skin lesions. A remission of histopathology characteristics of skin and nephritis was also observed upon IL-38 treatment. Accordingly, IL-38 receptor was expressed on the cell surface of both CD4+ Th and CD19+ B lymphocytes. The splenic Th17 and DN T lymphocytes, the average mRNA level of epigenetically regulated gene expression of Th17 cells, and serum concentrations of IL-17 and IL-22 were significantly decreased upon the treatment of IL-38 (all p<0.05). The in vivo results suggest that IL-38 can ameliorate skin inflammation and nephritis in SLE mice probably via suppressing the formation of inflammatory cytokines such as IL-17 and IL-22, and pathogenic DN T cells. These findings may provide a biochemical basis for further investigation of the therapeutic mechanisms of IL-38 for the treatment of autoimmune-mediated inflammation.
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