title: IL-23 induces receptor activator of NF-kappaB ligand expression on CD4+ T cells and promotes osteoclastogenesis in an autoimmune arthritis model.
abstract: IL-23, a clinically novel cytokine, targets CD4(+) T cells. Recent IL-1Ra(-/-) mouse studies have demonstrated that IL-23 indirectly stimulates the differentiation of osteoclast precursors by enhancing IL-17 release from CD4(+) T cells. IL-17, in turn, stimulates osteoclastogenesis in osteoclast precursor cells. In this study, we found that IL-23 up-regulates receptor activator of NF-kappaB ligand expression by CD4(+) T cells, and thus contributes to osteoclastogenesis. This indirect pathway is mediated by NF-kappaB and STAT3. We have also demonstrated that IL-23 can influence osteoclastogenesis positively under the special conditions in the IL-1-dominant milieu of IL-1Ra(-/-) mice. We propose that IL-23-enhanced osteoclastogenesis is mediated mainly by CD4(+) T cells. The results of this study show that IL-23 is a promising therapeutic target for the treatment of arthritis-associated bone destruction.
authors.affiliation: The Center for Rheumatic Diseases, Kangnam St Mary's Hospital, and Rheumatism Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Ji Hyeon
authors.initials: JH
authors.lastname: Ju
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
authors.forename: Young-Mee
authors.initials: YM
authors.lastname: Moon
authors.forename: Hye-Joa
authors.initials: HJ
authors.lastname: Oh
authors.forename: Jin-Sil
authors.initials: JS
authors.lastname: Park
authors.forename: Joo-Youn
authors.initials: JY
authors.lastname: Jhun
authors.forename: So-Youn
authors.initials: SY
authors.lastname: Min
authors.forename: Young-Gyu
authors.initials: YG
authors.lastname: Cho
authors.forename: Kyung-Su
authors.initials: KS
authors.lastname: Park
authors.forename: Chong-Hyeon
authors.initials: CH
authors.lastname: Yoon
authors.forename: Jun-Ki
authors.initials: JK
authors.lastname: Min
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Park
authors.forename: Young-Chul
authors.initials: YC
authors.lastname: Sung
authors.forename: Ho-Youn
authors.initials: HY
authors.lastname: Kim
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018450:Disease Progression; D053759:Interleukin-23 / Q000276:immunology / Q000378:metabolism*; D007596:Joints / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D053245:RANK Ligand / Q000276:immunology / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000276:immunology / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D053759:Interleukin-23; D016328:NF-kappa B; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse