Roles of basophil as a candidate to mediate the innate-adaptive link for Th2 responses.
| Project/Area Number |
17607005
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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 |
アレルギー
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| Research Institution | SHINSHU UNIVERSITY |
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Principal Investigator |
HIDA Shigeaki SHINSHU UNIVERSITY, Graduate School of Medicine, Assistant, 大学院医学研究科, 助教 (10345762)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAMOTO Masaya SHINSHU UNIVERSITY, Graduate School of Medicine, lecturer, 大学院医学研究科, 講師 (90226928)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | basophils / Th2 / inteleukin-3 / interleukin-4 / IRF-2 / signaling / IgE |
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| Research Abstract |
The initiation of adaptive immune responses is controlled by innate immune recognition. By contrast with Th1 type adaptive immune responses, the role of innate immunity in the development of Th2 type immune responses is still not well understood. Although basophiles are known to produce interleukin 4 (IL-4) and IL-6, the roles of these cells have been documented only in mice infected with parasites or in the effector phase of allergic inflammations. We found that both basophiles and IL-4 derived from them were indeed essential for Th2 development under neutral conditions in vitro. These results indicated that basophiles acted as a cellular converter to turn the neutral IL-3 into the Th2-inducing IL-4 during the initiation of Th1/Th2 differentiation. Furthermore, we showed that naive mice lacking the transcription factor, interferon regulatory factor 2 (IRF-2), exhibited signal transducer and activator of transcription 6 (Stat6)-independent expansion of basophiles in the periphery. Spontaneous Th2 polarization of CD4+ T cells was observed in these mice and the genetic reduction of basophil numbers by mutating the Kit gene abolished such a polarization in vivo. Thus, the negative regulatory role of IRF-2 on the basophil population size is critically important for preventing excess Th2 polarization and the Th1/Th2 balance in naive animals. On the other hand, studies on the IL-3 signaling in basophiles have been focused almost exclusively on its role in cell proliferation, and information for IL-3 signals mediating cytokine expression is limited. We found here that IL-4 production by spleen and bone marrow basophiles in response to IL-3 was severely impaired in mice lacking Fc receptor γ-chain (FcRγ-/-mice). Our findings revealed a previously unknown role of FcRγ in an IL-3 signaling pathway diverged downstream of Stat5, which leads to cytokine production, but not proliferation.
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Report
(3 results)
Research Products
(9 results)
