Significance and regulatory mechanisms of Fas/Fas L expression in the process of epidermal injury mediated by T cells
Significance and regulatory mechanisms of Fas/Fas L expression in the process of epidermal injury mediated by T cells
批准号:
09470191
负责人:
SHIOHARA Tetsuo
金额:
$6.91万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B)
财政年份:
1997
资助国家:
日本
项目状态:
已结题
起止时间:
1997 至 1998
中文摘要
We previously established a murine model for cutaneous graft-versus-host disease (GVHD) in which selective destruction of epidermal structure can be induced by local injection of Oracle D1+ Oracle D1, CD4 Oracle D1 + Oracle D1 autoreactive T cells capable of invading and destroying the epidermis in a site-restricted manner。在这个自定义的GVHD中,流行病自然地从破坏行为中恢复过来成为抵抗力,从而引起了对GVHD的间接攻击。在这一研究中,我们问了哪些FAS/FAS L交互可能会被纳入GVHD的定义和对自定义GVHD的抵抗的从属定义。我们的免疫组织化学研究和PCR分析演示了Fasantigen在不同GVHD期间表达了角蛋白中的视网膜菌,以及在Spontaneous恢复后也表达了角蛋白; Fas L-接受角蛋白在GVHD期间也观察到,但不是在Spontaneous恢复后。被注射的自动活性T细胞在bo上找到了快速的Fas和Fas L ... More 时间点。这些表达在蛋白质和mRNA水平上得到证实。我们下一次调查了GVHD和辅助抵抗在恢复后可能会受到LPR和Gld老鼠的影响,因为他们显然会在基因编码Fas和Fas L中受到影响,尊重。还有,GVHD在B6 LPR/LPR老鼠中也受到了影响,这个等级比控制老鼠少得多。利益是因为抵抗力从来没有在自发恢复后受到那些LPR老鼠的启发。在对比度下,GVHD对印度的能力和抵抗力没有在这些凝胶微观中受到影响。我们下一个被问到单克隆抗体(mAb)可能影响GVHD课程和抵抗力指数的问题。用抗Fas L mAb注射被边缘抑制了GVHD的诱导,而抵抗力的诱导完全被注入反Fas L mAb预防了。这些结果表明,Fas/Fas L相互作用在诱导GVHD抵抗力方面发挥了重要作用,而不是在诱导GVHD上,以及在遗传角质细胞上的FAS表达服务允许Fas L-轴承的自动攻击T细胞破坏他们。Less(低)
英文摘要
We previously established a murine model for cutaneous graft-versus-host disease (GVHD) in which selective destruction of epidermal structures can be induced by local injection of αβィイD1+ィエD1, CD4ィイD1+ィエD1 autoreactive T cells capable of invading and destroying the epidermis in a site-restricted manner. In this custaneous GVHD, the epidermis spontaneously recovered from the destruction became resistant to subsequent attempt to induce the GVHD. In this study, we asked whether Fas/Fas L interactions could be involved in the induction of the GVHD and the subsequent induction of the resistance to the custaneous GVHD.1. Our immunohistochemical studies and PCR analyses demonstrated that Fas antigen was expressed on keratinocytes in the lesional epidermis during the cutaneous GVHD and after spontaneous recovery; and Fas L-bearing keratinocytes were also observed during the GVHD but not after spontaneous recovery. The injected autoreactive T cells were found to express both Fas and Fas L at bo … More th time points. These expression was confirmed at protein and mRNA levels.2. We next investigated whether the GVHD and the subsequent resistance after recovery could be induced in lpr and gld mice which have been shown to have defects in the genes encoding Fas and Fas L, respectively. Although the GVHD was also induced in B6 lpr/lpr mice, the grade was much less prominent than control mice. Of interest was that the resistance was never induced in those lpr mice after spontaneous recovery. In contrast, the ability to induce GVHD and the resistance was not impaired in these gld mice.3. We next asked whether monoclonal antibodies (mAb) to Fas L could affect the course of GVHD and the induction of the resistance. Injection with anti-Fas L mAb marginally inhibited the induction of GVHD, while the induction of the resistance was totally prevented by injection of anti-Fas L mAb. These results indicate that Fas/Fas L interactions play an important role in inducing the GVHD resistance rather than inducing GVHD and that Fas expression on lesional keratinocytes serves to allow their destruction by Fas L-bearing autoaggressive T cells. Less
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Shiohara,T.et al.: "Human herpesvirus 6 infection as a risk factor for the development of severe druq-induiced hypersensitibity syrdrome"Arch. Dermatol. 134(9). 1108-1112 (1998)
Shiohara,T.et al.:“人类疱疹病毒 6 感染是严重 druq 诱发的超敏综合征发展的危险因素”Arch。
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Shiohara,T.et al.: "Cellular and molecular dynamics in exercise-induced urhearial vasculitis lisions."Aroh. Dermatol. B4(1). 62-67 (1998)
Shiohara,T.et al.:“运动诱发的尿道血管炎损伤中的细胞和分子动力学。”Aroh。
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Teraki Y, Shiohara T: "Apoptosis and the skin"Eur J Dermatol. (in press).
Teraki Y、Shiohara T:“细胞凋亡和皮肤”Eur J Dermatol。
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Shiohara,T.et al.: "Distinct in vivo and in vitro cytokine profiles of draining lymph node cells in aoute and chronic phases of contact hypersensitivity" J.Immunol.(in press). (1999)
Shiohara,T.et al.:“接触性超敏反应急性期和慢性期引流淋巴结细胞的不同体内和体外细胞因子谱”J.Immunol.(出版中)。
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Shiohara,T.et al.: "Epidermal T cells:their functional role and disease relevance for dermatologists" J.Invest.Dermatology. 109. 271-275 (1997)
Shiohara, T. 等人:“表皮 T 细胞:它们的功能作用和与皮肤科医生的疾病相关性”J.Invest.Dermatology。
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共 13 条
Analysis of factors that regulate effector T cell and regulatory T cell recruitment to the skin
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项目类别:Grant-in-Aid for Scientific Research (B)
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资助金额:$11.65万
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财政年份:2009
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负责人:SHIOHARA Tetsuo
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依托单位:
Regulation of skin-directed migration of regulatory T cells by fucosyltransferase
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Analysis of mechanisms by which CD8^+ T cells differentiate into the skin-homing phenotype
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批准号:15390344
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财政年份:2003
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The role for intraepidermal T cells as innate immune cells
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批准号:13470175
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项目类别:Grant-in-Aid for Scientific Research (B)
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资助金额:$8.32万
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财政年份:2001
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依托单位:
Mechanisms by which fucosyltransferases regulate epidermotropic migration of T cels
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批准号:11470184
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项目类别:Grant-in-Aid for Scientific Research (B).
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资助金额:$8.06万
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财政年份:1999
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负责人:SHIOHARA Tetsuo
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依托单位:
Functions and activation mechanisms of epidermal T cells.
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批准号:06454318
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项目类别:Grant-in-Aid for General Scientific Research (B)
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资助金额:$4.67万
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财政年份:1994
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负责人:SHIOHARA Tetsuo
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依托单位:
Molecular mechanism for homing of T cells to the epidermis
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批准号:04454288
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项目类别:Grant-in-Aid for General Scientific Research (B)
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资助金额:$4.35万
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财政年份:1992
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依托单位:
Analysis of Mechanisms by Which T Cells Migrate to the Epidermis
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批准号:01480268
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项目类别:Grant-in-Aid for General Scientific Research (B)
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资助金额:$4.03万
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财政年份:1989
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依托单位:
Analysis of factors relevant to the therapies for immunologically mediated skin diseases.
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批准号:63044130
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项目类别:Grant-in-Aid for Overseas Scientific Survey.
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资助金额:$1.6万
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财政年份:1988
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负责人:SHIOHARA Tetsuo
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依托单位:
Analysis of Pathogenesis of lichenoid tissue reactions
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批准号:62570461
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项目类别:Grant-in-Aid for General Scientific Research (C)
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资助金额:$1.22万
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财政年份:1987
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负责人:SHIOHARA Tetsuo
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依托单位:
国内基金
海外基金
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