Regulatory role of DC-derived osteopontin in systemic allergen sensitization.
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.
Kurokawa
Masatsugu
M
Johns Hopkins Asthma and Allergy Center, Baltimore, MD, USA.
Konno
Satoshi
S
Takahashi
Ayumu
A
Plunkett
Beverly
B
Rittling
Susan R
SR
Matsui
Yutaka
Y
Kon
Shigeyuki
S
Morimoto
Junko
J
Uede
Toshimitsu
T
Matsukura
Satoshi
S
Kokubu
Fumio
F
Adachi
Mitsuru
M
Nishimura
Masaharu
M
Huang
Shau-Ku
SK
D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology*; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D010047:Ovalbumin / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology
D000485:Allergens; D007074:Immunoglobulin G; D018793:Interleukin-13; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D053495:Osteopontin; D018664:Interleukin-12; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin