Yoshihara Kazufumi, Yamada Hisakata, Hori Akiko, Yajima Toshiki, Kubo Chiharu, Yoshikai Yasunobu
Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Eur J Immunol. 2007 Oct;37(10):2744-52. doi: 10.1002/eji.200737229.
IL-15 is thought to be involved in the pathogenesis of rheumatoid arthritis (RA). We found that IL-15 plays an important role in the development of murine collagen-induced arthritis (CIA). The incidence and severity of CIA were slightly decreased in IL-15 KO mice but were increased in IL-15 Tg mice compared with wild-type (WT) mice. The levels of type II collagen (CII)-specific IL-17 production were significantly increased in IL-15 Tg mice compared with WT mice with CIA. Expression of IL-23R was up-regulated in CD4(+) T cells in IL-15 Tg mice but down-regulated in IL-15 KO mice compared with WT mice. In correlation with the expression levels of IL-23R, IL-17 production by CD4(+) T cells in response to exogenous IL-23 was increased in IL-15 Tg mice compared with WT mice. Furthermore, exogenous IL-15 synergized with IL-23 to induce CII-specific IL-17 production by CD4(+) T cells in vitro. Taken together, these results indicate that IL-15 plays an important role in the progression of CIA through increasing antigen-specific IL-17 production by CD4(+) T cells.
白细胞介素-15（IL-15）被认为参与类风湿性关节炎（RA）的发病机制。我们发现IL-15在小鼠胶原诱导性关节炎（CIA）的发展中起重要作用。与野生型（WT）小鼠相比，IL-15基因敲除（KO）小鼠的CIA发病率和严重程度略有降低，而IL-15转基因（Tg）小鼠的发病率和严重程度则有所增加。与患有CIA的WT小鼠相比，IL-15 Tg小鼠中II型胶原（CII）特异性IL-17的产生水平显著增加。与WT小鼠相比，IL-15 Tg小鼠CD4(+) T细胞中IL-23R的表达上调，而IL-15 KO小鼠中则下调。与IL-23R的表达水平相关，与WT小鼠相比，IL-15 Tg小鼠中CD4(+) T细胞对外源性IL-23的反应产生的IL-17增加。此外，外源性IL-15与IL-23协同作用，在体外诱导CD4(+) T细胞产生CII特异性IL-17。综上所述，这些结果表明IL-15通过增加CD4(+) T细胞产生抗原特异性IL-17在CIA的进展中起重要作用。
