Histone deacetylases inhibitor Trichostatin A ameliorates DNFB-induced allergic contact dermatitis and reduces epidermal Langerhans cells in mice.
Histone deacetylases inhibitor Trichostatin A ameliorates DNFB-induced allergic contact dermatitis and reduces epidermal Langerhans cells in mice.
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DOI：
10.1016/j.jdermsci.2012.09.001
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发表时间：
2012-11
影响因子：
4.6
通讯作者：
Mi QS
中科院分区：
文献类型：
--
作者：
Shi YL;Gu J;Park JJ;Xu YP;Yu FS;Zhou L;Mi QS
组蛋白脱乙酰酶 (HDAC) 影响染色质组织，代表细胞中关键的表观遗传调控机制。 Trichostatin A (TSA) 是一种有效的 HDAC 抑制剂，具有抗肿瘤和抗炎作用。过敏性接触性皮炎 (ACD) 是一种 T 细胞介导的皮肤炎症反应，受表皮朗格汉斯细胞 (LC) 调节。本研究的目的是调查 TSA 治疗是否可以预防 2,4-二硝基氟苯 (DNFB) 诱导的小鼠 ACD，并在 ACD 发育过程中调节表皮 LC 和其他免疫细胞。 ACD 是通过局部 DNFB 致敏和激发来诱导的。在 ACD 诱导之前和期间，每隔一天用 TSA 或载体 DMSO 腹膜内治疗小鼠作为对照。测量耳朵肿胀反应并获取敏感皮肤区域的皮肤活检用于组织学分析。收集表皮细胞、胸腺、脾脏和皮肤引流淋巴结进行免疫染色。 TSA 治疗改善了 DNFB 诱导的 ACD 皮肤损伤的严重程度。在 TSA 处理的小鼠中，表皮 LC 和脾 DC 的百分比以及 LC 成熟均显着降低。然而，TSA治疗并没有显着影响胸腺、脾脏和引流淋巴结（dLN）中常规CD4+和CD8+T细胞、Foxp3+CD4+调节性T细胞、iNKT细胞和γδT细胞的稳态。此外，TSA 和 DMSO 处理的小鼠之间产生 IL-4 和 IFN-γ 的 T 细胞和 iNKT 细胞没有显着差异。我们的研究结果表明，TSA 可能通过调节表皮 LC 来改善 ACD，而 HDAC 可以作为 ACD 和其他 LC 相关皮肤病的潜在治疗靶点。
Histone deacetylases (HDACs) influence chromatin organization, representing a key epigenetic regulatory mechanism in cells. Trichostatin A (TSA), a potent HDAC inhibitor, has anti-tumor and anti-inflammatory effects. Allergic contact dermatitis (ACD) is a T-cell-mediated inflammatory reaction in skin and is regulated by epidermal Langerhans cells (LCs). The aim of this study was to investigate if TSA treatment prevents 2,4-dinitrofluorobenzene (DNFB)-induced ACD in mice and regulates epidermal LCs and other immune cells during ACD development. ACD was induced by sensitizing and challenging with DNFB topically. Mice were treated intraperitoneally with TSA or vehicle DMSO as a control every other day before and during induction of ACD. The ear swelling response was measured and skin biopsies from sensitized skin areas were obtained for histology. Epidermal cells, thymus, spleens and skin draining lymph nodes were collected for immune staining. TSA treatment ameliorated skin lesion severity of DNFB-induced ACD. The percentages of epidermal LCs and splenic DCs as well as LC maturation were significantly reduced in TSA-treated mice. However, TSA treatment did not significantly affect the homeostasis of conventional CD4+ and CD8+ T cells, Foxp3+CD4+ regulatory T cells, iNKT cells, and γδ T cells in thymus, spleen and draining lymph nodes (dLNs). Furthermore, there were no significant differences in IL-4 and IFN-γ-producing T cells and iNKT cells between TSA- and DMSO-treated mice. Our findings suggest that TSA may ameliorate ACD through the regulation of epidermal LCs and HDACs could serve as potential therapeutic targets for ACD and other LCs-related skin diseases.
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DOI：
10.1084/jem.20071966
发表时间：
2007-12-24
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bursch LS;Wang L;Igyarto B;Kissenpfennig A;Malissen B;Kaplan DH;Hogquist KA
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DOI：
10.4049/jimmunol.1001802
发表时间：
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期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
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通讯作者：
Kaplan DH
影响因子：
64.8
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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