Open AccessIL-23 Induces Receptor Activator of NF-κB Ligand Expression on CD4+ T Cells and Promotes Osteoclastogenesis in an Autoimmune Arthritis Model
Author(s) -
Ji Hyeon Ju,
MiLa Cho,
Young Myoung Moon,
Hyeyoung Oh,
JinSil Park,
Joo-Youn Jhun,
Sung−Wook Min,
Young-Gyu Cho,
Kyung-Su Park,
ChongHyeon Yoon,
JunKi Min,
Sung-Hwan Park,
YoungChul Sung,
Ho-Youn Kim
Publication year - 2008
Publication title -
the journal of immunology/the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.181.2.1507
Subject(s) - osteoclast , activator (genetics) , nf κb , receptor , chemistry , cytokine , microbiology and biotechnology , arthritis , cancer research , signal transduction , immunology , biology , biochemistry
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.