2011 Fiscal Year Final Research Report
The role of osteopontin in the generation of memory CD8 T cells during influenza virus infection
| Project/Area Number |
22790449
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | Hokkaido University |
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Principal Investigator |
MORIMOTO Junko 北海道大学, 遺伝子病制御研究所, 助教 (20451396)
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| Project Period (FY) |
2010 – 2011
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| Keywords | 免疫記憶 / ウイルス感染 |
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| Research Abstract |
The adaptive immune system generates memory cells, which induce a rapid and robust immune response following secondary antigen encounter. Memory CD8^+T cells are a critical component of protective immunity against infections and cancers. Therefore, understanding the mechanism whereby memory CD8^+T cells are generated and maintained is important for inducing effective memory CD8^+T cell response. Recent studies have demonstrated that the inflammatory cytokine IL-12 favors the generation of terminal effector CD8^+T cells rather than memory precursor effector CD8^+T cells by regulating the expression of the transcription factor T-bet. In this study, we report that the inflammatory cytokine osteopontin(Opn) modulates memory CD8^+T cell generation during influenza virus infection. Although Opn-wild-type(Opn WT) and Opn-knockout(Opn KO) mice had similar numbers of virus-specific effector CD8^+T cells, virus-specific effector CD8^+T cells generated in Opn KO mice showed low levels of T-bet expression and an increased memory precursor cell population compared with cells generated in Opn WT mice. This resulted in the persistently increased number of memory CD8^+T cells in Opn KO mice. Studies with bone marrow-derived dendritic cells(BMDCs) demonstrated that Opn-deficiency in BMDCs results in low levels of IL-12 production in response to the stimulation with influenza virus. Thus, we hypothesize that Opn modulates the generation of memory precursor effector CD8^+T cells by regulating cytokine milieu during the acute phase of virus infection. This finding may provide new insight into the role of Opn in adaptive immune response.
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Author(s)
Ikesue M., Matsui Y., Ohta D., Danzaki K., Ito K., Kanayama M., Kutotaki D., Morimoto J., Kojima T., Tsutsui H., Uede T.
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Journal Title
Arterioscler Thromb Vasc Biol
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[Journal Article] CSF-1-dependent red pulp macrophages regulate CD4 T cell responses2011
Author(s)
Kurotaki D., Kon S., Bae K., Ito K., Matsui Y., Nakayama Y., Kanayama M., Kimura C., Narita Y., Nishimura T., Iwabuchi K., Mack M., Van Rooijen N., Sakaguchi S., Uede T., Morimoto J
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Journal Title
J Immunol
Volume: 186(4)
Pages: 2229-2237
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[Journal Article] Prevention of experimental autoimmune uveoretinitis by blockade of osteopontin with small interfering RNA2010
Author(s)
Iwata D, Kitamura M, Kitaichi N, Saito Y, Kon S, Namba K, Morimoto J, Ebihara A, Kitamei H, Yoshida K, Ishida S, Ohno S, Uede T, Onoe K, and Iwabuchi K
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Journal Title
Exp. Eye Res
Volume: 90(1)
Pages: 41-48
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