2006 Fiscal Year Final Research Report Summary
Mechanisms underlying IL-4-induced IFN-γ production in plasmacytoid dendritic cells
| Project/Area Number |
17591029
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | Chiba University |
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Principal Investigator |
NAKAJIMA Hiroshi Chiba University, Molecular Genetics, Professor, 大学院医学研究院, 教授 (00322024)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Norihiko Chiba University Hospital, Allergy and Clinical Immunology, Assistant Professor, 医学部附属病院, 講師 (20375653)
KAGAMI Shin-ichiro Chiba University, Molecular Genetics, Assistant Professor, 大学院医学研究院, 助手 (30375654)
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| Project Period (FY) |
2005 – 2006
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| Keywords | plasmacytoid dendritic cells / IL-4 / IFN-γ / Stat6 / Stat4 / Th2 cell suppression |
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| Research Abstract |
Cytokine environment is critical for the differentiation and commitment of immune cells. For example, IL-4, a representative Th2 cytokine, induces further Th2 cell differentiation, whereas a Th1 cytokine IFN-γ in coordination with IL-12 induces Th1 cell differentiation. While these positive-feedback mechanisms are essential for the profound differentiation of T helper cells, the immune system also has a number of intrinsic and extrinsic machinery to antagonize the excessive differentiation of immune cells.
We show in this research that IL-4 induces IFN-γ production in B22O^+ plasmacytoid dendritic cells (PDCs). By searching for cell populations that produce IFN-γ upon IL-4 stimulation, we found that PDCs were a major IFN-γ-producing cell upon IL-4 stimulation in wild-type and Rag-2^<-/-> splenocytes. Isolated PDCs, but not CD11b^+ DCs or CD8^+ DCs, produced IFN-γ upon IL-4 stimulation. In vivo, the depletion of PDCs by anti-Ly6G/C antibody prevented IFN-γ production induced by IL-4 administration. We also found that IL-4 induced IFN-γ production, but not IL-12 or IFN-α production, in PDCs and also strongly enhanced CpG ODN-induced IFN-γ production, but not CpG ODN-induced IL-12 or IFN-a production. However, IL-4 did not induce IFN-γ production in Stat6^<-/->PDCs. Moreover, IL-4 induced Stat4 expression in PDCs through a Stat6-dependent mechanism and only the Stat4-expressing PDCs produced IFN-γ. Furthermore, IL-4 did not induce IFN-γ production in Stat4^<-/->PDCs. These results indicate that PDCs preferentially produce IFN-γ upon IL-4 stimulation by Stat6- and Stat4-dependent mechanisms.
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[Journal Article] IL-25 enhances allergic airway inflammation by amplifying a Th2 cell-dependent pathway in mice.2006
Author(s)
Tamachi T, Maezawa Y, Ikeda K, Kagami S, Hatano M, Seto Y, Suto A, Suzuki K, Watanabe N, Saito Y, Tokuhisa T, Iwamoto I, Nakajima H.
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Journal Title
J. Allergy Clin. Immunol. 118
Pages: 606-614
Description
「研究成果報告書概要(欧文)」より
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