IL-15 exacerbates collagen-induced arthritis with an enhanced CD4+ T cell response to produce IL-17.
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.
Yoshihara
Kazufumi
K
Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Yamada
Hisakata
H
Hori
Akiko
A
Yajima
Toshiki
T
Kubo
Chiharu
C
Yoshikai
Yasunobu
Y
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002478:Cells, Cultured; D024043:Collagen Type II / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D019409:Interleukin-15 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020381:Interleukin-17 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic