| Project/Area Number |
18591233
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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 | Kyoto University (2007)
Gunma University (2006) |
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Principal Investigator |
NAKAMURA Motonobu Kyoto University, Department ofDermatology, Associate Professor (30303837)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Alopecia areata / Th1 / siRNA / C3H / HeJ mouse / siRNA / siRNA3 / T-bet / アンチセンスオリゴヌクレオチド / FITC |
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| Research Abstract |
Autoimmune alopecia (alopecia areata) is considered to be triggered by a collapse of immune privilege in hair follicles. Here we confirmed that infiltrating lymphocytes around the hair follicles of alopecia areata were mostly CD4,CCR5 double positive with few CD4,CCR4 double positive cells suggesting a dominant role of Th1 cells in the alopecic lesion. Local injections of interleukin (IL) -4 or neutralizing antibody against interferon (IFN)-γ were effective for alopecia in C3H/HeJ mice, a mouse model for alopecia areata. Semiquantitative RT-PCR assay demonstrated that intralesional injection of IL-4 suppressed the enhanced IFN-γ mRNA expression in the alopecic skin. Furthermore, Th1 transcription factor T-bet small interfering RNA (siRNA) applications conjugated with cationized gelatin repressed the T-bet expression and showed restoring effects on alopecia in C3H/HeJ mice. MHC class I and II molecules expression in the follicular epithelium was diminished by the T-bet siRNA injections, indicating a restoration of immune privilege. Taken together, the new controlled drug delivery system for siRNA conjugated with gelatin can be a novel candidate for promising therapeutic approaches to various human diseases and cancers.
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