Regulatory role of DC‐derived osteopontin in systemic allergen sensitization |
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| Authors: | Masatsugu Kurokawa Satoshi Konno Ayumu Takahashi Beverly Plunkett Susan R Rittling Yutaka Matsui Shigeyuki Kon Junko Morimoto Toshimitsu Uede Satoshi Matsukura Fumio Kokubu Mitsuru Adachi Masaharu Nishimura Shau‐Ku Huang |
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| Institution: | 1. Johns Hopkins Asthma and Allergy Center, Baltimore, MD, USA;2. Division of Respiratory Medicine and Allergology, Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan;3. First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan;4. Department of Genetics, Rutgers University, Piscataway, NJ, USA;5. Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan;6. Department of Matrix Medicine, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan;7. Department of Respiratory Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan |
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| Abstract: | 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. |
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| Keywords: | Bone marrow‐derived DC IgE Osteopontin Th2 cytokines |
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