title: [Regulation of inflammation through JAK3-Stat6 pathway in dendritic cells].
abstract: Dendritic cells (DCs) is the cell that act as source of the immune response by exquisitely presenting antigens to acquired immunity such as the T cells. Janus kinase (JAK) is a tyrosine kinase that is activated immediately after the cytokine binds to its unique receptor expressed on the cell surface. Among the JAKs, expression of JAK3 is limited on haematopoietic cells and is indispensable for lymphocyte development and proliferation. We have demonstrated that JAK3-deficient DCs normally develop, uptake antigens, produce inflammatory cytokines and function as an antigen-presenting cell, although they over-produce IL-10. Among the transcription factors that are known to be activated by JAK3, we explored the phenotype of Stat6-deficient DCs which is a transcription factor specifically activated by JAK3. Interestingly, development, function and inflammatory cytokine production was normal with over-production of IL-10 which was in line with the JAK3-deficient DCs. IL-4 is well known to activate JAK3-Stat6 in the cytoplasm and has been reported to be produced in the synovial fluid of rheumatoid arthritis patients. Hence the suppression of IL-10 production by IL-4 can be considered as one of the inflammatory process of arthritis. Moreover, induction of IL-10 production by DCs can be one mechanism of action of the JAK inhibitor (tofacitinib) which have shown high efficiency on active rheumatoid arthritis in clinical trials.
authors.affiliation: The First Department of Internal Medicine, School of Medicine, University of Occupational and Enviromental Health, Kitakyushu, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yamaoka
authors.forename: Keisuke
authors.initials: K
authors.lastname: Maeshima
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kubo
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology; D053616:Janus Kinase 3 / Q000276:immunology / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D007378:Interleukins; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D053616:Janus Kinase 3