Skin application of ketoprofen systemically suppresses contact hypersensitivity by inducing CD4+ CD25+ regulatory T cells
Skin application of ketoprofen systemically suppresses contact hypersensitivity by inducing CD4+ CD25+ regulatory T cells
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DOI：
10.1016/j.jdermsci.2008.10.011
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发表时间：
2009-03-01
影响因子：
4.6
通讯作者：
Tokura, Yoshiki
中科院分区：
文献类型：
--
作者：
Atarashi, Kenji;Mori, Tomoko;Tokura, Yoshiki
背景：酮洛芬（KP）是一种广泛应用的非甾体抗炎药，可抑制前列腺素的生物合成。我们以前已经表明，局部KP治疗的致敏部位抑制发展的接触超敏反应（CHS）苦氯（PCl.Objective）：我们研究了潜在的机制KP诱导的免疫抑制CHS的应用KP。方法：我们分析了CHS对非致敏位点的反应和随后的PCl致敏，以及通过将引流淋巴结细胞（LNC）从KP耐受小鼠转移到受体小鼠。Foxp 3表达的变化从KP-光处理的皮肤LNCs也检查通过real-time PCR.Results：局部应用KP不仅敏化，但也非敏化网站抑制CHS反应。免疫抑制用来自用PCl加KP处理的小鼠的LNC转移，但不来自恶唑酮加KP处理的小鼠。在本转移研究中，CD 4（+）CD 25（+）亚群的LNC发挥了抑制作用，而CD 25（+）细胞缺失的LNC失去了抑制能力。用特异性抗体阻断CTLA-4，而不是IL-10阻断，消除了CD 4（+）CD 25（+）细胞的活性。结论：KP局部应用对CHS的免疫抑制作用具有系统性和抗原特异性。Treg细胞在KP的抑制作用中起重要作用。(C)2008年日本皮肤病研究学会。由Elsevier爱尔兰有限公司出版。保留所有权利。
Background: Ketoprofen (KP) is a widely used nonsteroidal anti-inflammatory drug that inhibits prostaglandin biosynthesis. We have previously shown that topical KP treatment at the sensitizing site inhibits the development of contact hypersensitivity (CHS) to picryl chloride (PCl).Objective: We investigated the mechanism underlying the KP-induced immunosuppression of CHS by application of KP.Methods: We analyzed the CHS responses to the non-sensitizing site and subsequent sensitization with PCl, and by transfer of the draining lymph node cells (LNCs) from KP-tolerated mice to recipient mice. Changes in the Foxp3 expression of LNCs from KP-phototreated skin were also examined by real-time PCR.Results: Topical application of KP to not only the sensitizing but also non-sensitizing site suppressed CHS response. The immunosuppression was transferred with LNCs from mice treated with PCl Plus KP, but not from mice treated oxazolone plus KP. In this transfer study, the CD4(+) CD25(+) subset of LNCs exerted the suppressive effect, while CD25(+) cell-depleted LNCs lost the inhibitory ability. CTLA-4 blocking with a specific antibody, but not IL-10 blocking, abrogated the activity of CD4(+) CD25(+) cells. Moreover, Foxp3 mRNA expression was remarkably increased in LNCs from PCl and KP-treated mice.Conclusion: The immunosuppression of CHS by topical application of KP is systemic and haptein-specific. Treg cells play an important role in the suppressive effect by KP. (C) 2008 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.