2006 Fiscal Year Final Research Report Summary
Dysfunctional Blood and Target Tissue CD4^+CD25^<high> Regulatory T Cells in Psoriasis.
| Project/Area Number |
17591163
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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 | University of Yamanashi, Interdisciplinary Graduate School of Medicine and Engineering |
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Principal Investigator |
SUGIYAMA Hideaki University of Yamanashi, Department of Research Interdisciplinary Graduate School of Medicine and Engineering, Research Associate, 大学院医学工学総合研究部, 助手 (70301207)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMADA Shinji University of Yamanashi, Department of Research Interdisciplinary Graduate School of Medicine and Engineering, Professor, 大学院医学工学総合研究部, 教授 (10114505)
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| Project Period (FY) |
2005 – 2006
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| Keywords | psoriasis vulgaris / autoimmunity / regulatory T cell |
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| Research Abstract |
The balance between regulatory and effector functions is important for maintaining efficient immune responses, while avoiding autoimmunity. The inflammatory skin disease psoriasis is sustained by the ongoing activation of pathogenic effector T cells. We found that a CD4^+ T lymphocyte subpopulation in peripheral blood, phenotypically CD25^<high>, CTLA-4^+, Foxp3^<high> (regulatory T cells), is deficient in its suppressor activity in psoriasis. This was associated with accelerated proliferation of CD4^+ responder T cells in psoriasis, the majority of which expressed CXCR3. Nevertheless, criss-cross experiments isolated the defect to psoriatic regulatory T cells. To examine regulatory T cells in a non-lymphoid tissue of a human T cell-mediated disease, regulatory T cells were also analyzed and isolated from the site of inflammation, psoriatic lesional skin. At the regulatory vs. effector T cells ratios calculated to be present in the skin, however, the psoriatic regulatory T cell population demonstrated decreased suppression of effector T cells. Thus, dysfunctional blood and target tissue CD4^+CD25^<high> regulatory T cell activity may lead to reduced restraint, and consequent hyperproliferation of psoriatic pathogenic T cells in vivo. These findings represent a critical component of human organ-specific autoimmune disease, and may have important implications with regard to the possible therapeutic manipulation of regulatory T cells in vivo.
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