IL-23 induces receptor activator of NF-kappaB ligand expression on CD4+ T cells and promotes osteoclastogenesis in an autoimmune arthritis model.
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.
Ju
Ji Hyeon
JH
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.
Cho
Mi-La
ML
Moon
Young-Mee
YM
Oh
Hye-Joa
HJ
Park
Jin-Sil
JS
Jhun
Joo-Youn
JY
Min
So-Youn
SY
Cho
Young-Gyu
YG
Park
Kyung-Su
KS
Yoon
Chong-Hyeon
CH
Min
Jun-Ki
JK
Park
Sung-Hwan
SH
Sung
Young-Chul
YC
Kim
Ho-Youn
HY
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
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