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他克莫司软膏对特应性皮炎中调节性T淋巴细胞的影响。

The effects of tacrolimus ointment on regulatory T lymphocytes in atopic dermatitis.

作者信息

Caproni Marzia, Torchia Daniele, Antiga Emiliano, Volpi Walter, del Bianco Elena, Fabbri Paolo

机构信息

Department of Dermatological Sciences, University of Florence, Florence, Italy.

出版信息

J Clin Immunol. 2006 Jul;26(4):370-5. doi: 10.1007/s10875-006-9034-2. Epub 2006 Jun 14.

DOI:10.1007/s10875-006-9034-2
PMID:16773453
Abstract

Only very recently studies were conducted in order to evaluate the impact of regulatory T (Treg) cells in the pathophysiology of atopic dermatitis (AD). Nine adult patients with moderate-to-severe AD in riacutization period of a chronic disease were given tacrolimus ointment, while seven hydrocortisone butyrate ointment, that served as controls. We performed lesional-skin biopsies before and after treatment, that were stained immunohistochemically with monoclonal antibodies to CD4, CD25, forkhead/winged helix transcription factor (FoxP3), interleukin (IL)-10 and transforming growth factor (TGF)-beta. CD4+ cells were significantly reduced in post-treatment series. Tacrolimus treatment achieved a significant reduction of CD25+ cells. FoxP3+ cells were present in untreated AD lesions. Both treatments did not significantly modify the number of FoxP3+ cells. The number of IL-10+ cells increased in post-treatment series. Tacrolimus enhanced the production of TGF-beta, while hydrocortisone did not. Restoration of TGF-beta-producing Treg cells may represent another important pharmacodynamic effect of tacrolimus on AD.

摘要

直到最近才开展了一些研究,以评估调节性T(Treg)细胞在特应性皮炎(AD)病理生理学中的作用。9例处于慢性病急性发作期的中重度AD成年患者外用他克莫司软膏,7例外用丁酸氢化可的松软膏作为对照。我们在治疗前后进行皮损活检,并用抗CD4、CD25、叉头/翼状螺旋转录因子(FoxP3)、白细胞介素(IL)-10和转化生长因子(TGF)-β的单克隆抗体进行免疫组织化学染色。治疗后CD4+细胞显著减少。他克莫司治疗使CD25+细胞显著减少。未经治疗的AD皮损中存在FoxP3+细胞。两种治疗均未显著改变FoxP3+细胞数量。治疗后IL-10+细胞数量增加。他克莫司可增强TGF-β的产生,而氢化可的松则不能。恢复产生TGF-β的Treg细胞可能是他克莫司对AD的另一个重要药效学作用。

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本文引用的文献

1
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J Allergy Clin Immunol. 2006 Jan;117(1):176-83. doi: 10.1016/j.jaci.2005.10.040.
2
Sequential development of interleukin 2-dependent effector and regulatory T cells in response to endogenous systemic antigen.内源性全身抗原刺激下白细胞介素2依赖效应性和调节性T细胞的顺序发育
J Exp Med. 2005 Nov 21;202(10):1375-86. doi: 10.1084/jem.20050855. Epub 2005 Nov 14.
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Factors that regulate naturally occurring T regulatory cell-mediated suppression.
外用他克莫司成功治疗口周浆细胞增多症:两例报告及免疫组织化学研究
Case Rep Dermatol. 2013 Mar 20;5(1):79-83. doi: 10.1159/000350184. Print 2013 Jan.
4
Successful treatment of granuloma faciale with topical tacrolimus: a case report and immunohistochemical study.外用他克莫司成功治疗面部肉芽肿:一例报告及免疫组化研究
Case Rep Dermatol. 2012 May;4(2):158-62. doi: 10.1159/000341196. Epub 2012 Jul 12.
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Preventive and therapeutic effects of tacrolimus in an interleukin-10-deficient mouse model of colitis.他克莫司在白细胞介素-10 缺陷型结肠炎小鼠模型中的预防和治疗作用。
Inflamm Res. 2011 Nov;60(11):1049-59. doi: 10.1007/s00011-011-0366-x. Epub 2011 Aug 10.
6
CD4+ regulatory T cells in solid organ transplantation.实体器官移植中的 CD4+ 调节性 T 细胞。
Curr Opin Organ Transplant. 2010 Dec;15(6):757-64. doi: 10.1097/MOT.0b013e32834017ae.
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Latent simian varicella virus reactivates in monkeys treated with tacrolimus with or without exposure to irradiation.潜伏的猴痘病毒在接受他克莫司治疗的猴子中重新激活,无论是否暴露于辐射下。
J Neurovirol. 2010 Oct;16(5):342-54. doi: 10.3109/13550284.2010.513031.
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Immunology. 2007 Oct;122(2):149-56. doi: 10.1111/j.1365-2567.2007.02651.x.
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Interleukin-10-secreting "regulatory" T cells induced by glucocorticoids and beta2-agonists.由糖皮质激素和β2-激动剂诱导产生的分泌白细胞介素-10的“调节性”T细胞。
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Efficacy and tolerability of topical pimecrolimus and tacrolimus in the treatment of atopic dermatitis: meta-analysis of randomised controlled trials.外用吡美莫司和他克莫司治疗特应性皮炎的疗效及耐受性:随机对照试验的荟萃分析
BMJ. 2005 Mar 5;330(7490):516. doi: 10.1136/bmj.38376.439653.D3. Epub 2005 Feb 24.