title: In vivo anti-inflammatory activities of novel cytokine IL-38 in Murphy Roths Large (MRL)/lpr mice.
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.
authors: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
authors: Man
authors: M
authors: Chu
authors: Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
authors: Lai Shan
authors: LS
authors: Tam
authors: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
authors: Jing
authors: J
authors: Zhu
authors: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
authors: Delong
authors: D
authors: Jiao
authors: Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China; Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong.
authors: De Hua
authors: H
authors: Liu
authors: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
authors: Zhe
authors: Z
authors: Cai
authors: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
authors: Jie
authors: J
authors: Dong
authors: State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau.
authors: Christopher Wei
authors: CW
authors: Kai Lam
authors: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China; Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong. Electronic address: ck-wong@cuhk.edu.hk.
authors: Chun Kwok
authors: CK
authors: Wong
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D007378:Interleukins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D001323:Autoantibodies; D016207:Cytokines; D007378:Interleukins
keywords: Autoinflammatory disease; Cytokines; IL-38; Inflammation; Systemic lupus erythematosus; T cells