| Project/Area Number |
10670781
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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 |
Dermatology
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| Research Institution | Tokyo Medical and Dental University, Graduate school |
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Principal Investigator |
YOKOZEKI Hiroo Tokyo Medical and Dental University, Graduate school, Associate professor, 大学院・医歯学総合研究科, 助教授 (90210608)
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| Co-Investigator(Kenkyū-buntansha) |
SATOH Takahiro Tokyo Medical and Dental University, School of Medicine Assistant Professor, 医学部・附属病院, 講師 (30235361)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | STAT6 / Th2 / Contact Hypersensitivity / Hapten / Cytokine / Langerhans cells / ハプテン / IL-4 / IL-13 |
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| Research Abstract |
Contact hypersensitivity (CHS) is thought to be mainly associated with the activation of T-helper (Th) 1 cells. However, there is also evidence that Th2 cells or Th2 cytokines play a role in the development of CHS.In order to analyze the functional contribution of Th2 cvtokines, IL-4 and IL-13, STAT6 deficient (STAT6-/-) and wild-type control (wt) mice (C57BL/6) were contact sensitized with 5% TNCB, 0.5 % DNFB or 5% Oxa, and then any skin reactions were examined. Ear swelling was significantly reduced with a delayed peak response in STAT6-/- mice as compared with wt mice.
A histological analysis revealed that the infiltration of both eosinophils and neutrophils in the skin challenged after 24 h in STAT6-/- mice decreasead substantially in comparison with that in wt mice. The expression of Th2 cytokines (IL-4, IL-5 ) in TNCB-challenged skin tissues and the supernatants from T cells stimulated by TNBS -modified spleen cells as well as the IgE and IgG1 response after challenge were also profoundly reduced in STAT6-/- mice, whereas the expression of IFN γ was the same in STAT6-/- mice and wt mice after challenge. Furthermore, Adoptive transfer experiments revealed that STAT6-/- mice induced the contact hypersensitivity after injection of lymph node cells obtained from sensitized wt mice.
Our data suggest that the STAT6 signal palys a critical role in the i nductionphase of CHS.
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