TY - JOUR
T1 - Regulatory role of DC-derived osteopontin in systemic allergen sensitization
AU - Kurokawa, Masatsugu
AU - Konno, Satoshi
AU - Takahashi, Ayumu
AU - Plunkett, Beverly
AU - Rittling, Susan R.
AU - Matsui, Yutaka
AU - Kon, Shigeyuki
AU - Morimoto, Junko
AU - Uede, Toshimitsu
AU - Matsukura, Satoshi
AU - Kokubu, Fumio
AU - Adachi, Mitsuru
AU - Nishimura, Masaharu
AU - Huang, Shau Ku
PY - 2009/12
Y1 - 2009/12
N2 - Osteopontin (OPN) is a secreted phosphoglycoprotein with a wide range of functions, and is involved in various pathophysiological conditions. However, the role of OPN in IgE and Th2-associated allergic responses remains incompletely defined. The aim of this study was to elucidate the role of OPN in systemic allergen sensitization in mice. When compared with OPN+/+ mice, significantly increased levels of OVA-induced IgE were found in OPN -/- mice. OPN-/- DC demonstrated an increased capacity to enhance Th2 cytokine production in CD4+ T cells from sensitized OPN+/+ mice. Furthermore, significantly reduced levels of IL-12p70 expression were seen in LPS-stimulated OPN-/- DC as compared with the WT DC, and the reduction was reversible by the addition of recombinant OPN (rOPN). rOPN was able to suppress OVA-induced IL-13 production in the cultures of CD4 and OPN-/- DC, but this inhibitory activity was neutralized by the addition of anti-IL-12 Ab. In addition, administration of rOPN in vivo suppressed OVA-specific IgE production; however, this suppressive effect was abrogated in IL-12-deficient mice. These results indicate that DC-derived OPN plays a regulatory role in the development of systemic allergen sensitization, which is mediated, at least in part, through the production of endogenous IL-12.
AB - Osteopontin (OPN) is a secreted phosphoglycoprotein with a wide range of functions, and is involved in various pathophysiological conditions. However, the role of OPN in IgE and Th2-associated allergic responses remains incompletely defined. The aim of this study was to elucidate the role of OPN in systemic allergen sensitization in mice. When compared with OPN+/+ mice, significantly increased levels of OVA-induced IgE were found in OPN -/- mice. OPN-/- DC demonstrated an increased capacity to enhance Th2 cytokine production in CD4+ T cells from sensitized OPN+/+ mice. Furthermore, significantly reduced levels of IL-12p70 expression were seen in LPS-stimulated OPN-/- DC as compared with the WT DC, and the reduction was reversible by the addition of recombinant OPN (rOPN). rOPN was able to suppress OVA-induced IL-13 production in the cultures of CD4 and OPN-/- DC, but this inhibitory activity was neutralized by the addition of anti-IL-12 Ab. In addition, administration of rOPN in vivo suppressed OVA-specific IgE production; however, this suppressive effect was abrogated in IL-12-deficient mice. These results indicate that DC-derived OPN plays a regulatory role in the development of systemic allergen sensitization, which is mediated, at least in part, through the production of endogenous IL-12.
KW - Bone marrow-derived DC
KW - IgE
KW - Osteopontin
KW - Th2 cytokines
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U2 - 10.1002/eji.200838970
DO - 10.1002/eji.200838970
M3 - Article
C2 - 19830723
AN - SCOPUS:73249129192
SN - 0014-2980
VL - 39
SP - 3323
EP - 3330
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 12
ER -