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IL-23 Induces Receptor Activator of NF-B Ligand Expression on CD4⁺ T Cells and Promotes Osteoclastogenesis in an Autoimmune Arthritis Model¹

Ji Hyeon Ju^*, Mi-La Cho^*, Young-Mee Moon^*, Hye-Joa Oh^*, Jin-Sil Park^*, Joo-Youn Jhun^*, So-Youn Min^*, Young-Gyu Cho^*, Kyung-Su Park^*, Chong-Hyeon Yoon^*, Jun-Ki Min^*, Sung-Hwan Park^*, Young-Chul Sung and Ho-Youn Kim^2,*

^* 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; and Department of Life Science, Biotech Center, Pohang University of Science and Technology, Pohang, South Korea

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-B ligand expression by CD4⁺ T cells, and thus contributes to osteoclastogenesis. This indirect pathway is mediated by NF-B 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Grant R11-2002-098-05001-0 from the Korea Science & Engineering Foundation through the Rheumatism Research Center at The Catholic University of Korea.

² Address correspondence and reprint requests to Dr. Ho-Youn Kim, Rheumatism Research Center, Catholic Institute of Medical Science, The Catholic University of Korea, 505 Banpo-Dong, Seocho-Ku, Seoul 137–040, Korea. E-mail address: ho0919{at}catholic.ac.kr

³ Abbreviations used in this paper: RA, rheumatoid arthritis; RANK, receptor activator of NF-B; RANKL, RANK ligand; FLS, fibroblast-like synoviocyte; BMC, bone marrow cell; rAd, recombinant adenovirus; TRAP, tartrate-resistant acid phosphatase; eGFP, enhanced GFP; MMP, matrix metalloproteinase; siRNA, small interfering RNA; WT, wild type.