title: IL-27 suppresses RANKL expression in CD4+ T cells in part through STAT3.
abstract: The receptor activator of NF-κB ligand (RANKL), which is expressed by not only osteoblasts but also activated T cells, plays an important role in bone-destructive diseases such as rheumatoid arthritis. IL-27, a member of the IL-6/IL-12 family cytokines, activates STAT1 and STAT3, promotes early helper T (Th)1 differentiation and generation of IL-10-producing type 1 regulatory T (Tr1) cells, and suppresses the production of inflammatory cytokines and inhibits Th2 differentiation. In addition, IL-27 was recently demonstrated to not only inhibit Th17 differentiation but also directly act on osteoclast precursor cells and suppress RANKL-mediated osteoclastogenesis through STAT1-dependent inhibition of c-Fos, leading to amelioration of the inflammatory bone destruction. In the present study, we investigated the effect of IL-27 on the expression of RANKL in CD4(+) T cells. We found that IL-27 greatly inhibits cell surface expression of RANKL on naive CD4(+) T cells activated by T cell receptor ligation and secretion of its soluble RANKL as well. The inhibitory effect was mediated in part by STAT3 but not by STAT1 or IL-10. In contrast, in differentiated Th17 cells, IL-27 much less efficiently inhibited the RANKL expression after restimulation. Taken together, these results indicate that IL-27 greatly inhibits primary RANKL expression in CD4(+) T cells, which could contribute to the suppressive effects of IL-27 on the inflammatory bone destruction.
authors: Department of Clinical Sciences, Josai International University, 1 Gumyo, Togane, Chiba 283-8555, Japan.
authors: Sadahiro
authors: S
authors: Kamiya
authors: Masae
authors: M
authors: Okumura
authors: Yukino
authors: Y
authors: Chiba
authors: Takeshi
authors: T
authors: Fukawa
authors: Chika
authors: C
authors: Nakamura
authors: Noriyuki
authors: N
authors: Nimura
authors: Junichiro
authors: J
authors: Mizuguchi
authors: Seiki
authors: S
authors: Wada
authors: Takayuki
authors: T
authors: Yoshimoto
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects*; D007378:Interleukins / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D053245:RANK Ligand / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: C486767:Il27 protein, mouse; D007378:Interleukins; D053245:RANK Ligand; D011948:Receptors, Antigen, T-Cell; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor