Nonpathogenic bacteria alleviating atopic dermatitis inflammation induce IL-10-producing dendritic cells and regulatory Tr1 cells.
Nonpathogenic bacteria alleviating atopic dermatitis inflammation induce IL-10-producing dendritic cells and regulatory Tr1 cells.
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DOI：
10.1038/jid.2013.291
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发表时间：
2014
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影响因子：
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通讯作者：
T. Volz;Y. Skabytska;E. Guenova;Ko-Ming Chen;J. Frick;C. Kirschning;S. Kaesler;M. Röcken;T. Biedermann
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文献类型：
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作者：
T. Volz;Y. Skabytska;E. Guenova;Ko-Ming Chen;J. Frick;C. Kirschning;S. Kaesler;M. Röcken;T. Biedermann
非致病细菌的有益作用越来越受到人们的认可。我们在一项针对特应性皮炎 (AD) 患者的安慰剂对照研究中报告称，皮肤接触非致病性细菌裂解物可减轻皮肤炎症。为了揭示潜在的机制，我们对传感非病原性细菌丝状玻璃颤菌裂解物 (Vf) 的免疫后果进行了表征，分析 (1) 树突状细胞 (DC) 的分化，以及 (2) 体外 DC 和 T 辅助 (Th) 细胞的效应器功能以及体内 NC/Nga 小鼠 AD 小鼠模型中的效应功能。 Vf 局部治疗可显着减少 NC/Nga 小鼠的 AD 样炎症。重要的是，皮肤暴露于 Vf 与过敏原 FITC 的结合也显着减少了随后的过敏原诱发的皮炎，表明主动免疫调节。事实上，Vf 的先天感知主要诱导产生 IL-10 的 DC，这依赖于 Toll 样受体 2 (TLR2) 的激活。 Vf 诱导的 IL-10+ DC 使幼稚 CD4+ T 辅助细胞成为调节性 IFN-γlowIL-10highTr1（1 型调节性 T）细胞。这些 IL-10highTr1 细胞也由 Vfin vivo 诱导，并强烈抑制 T 效应细胞和炎症。总之，我们发现 TLR2 对非病原性细菌的先天感知会诱导耐受性 DC 和调节性 Tr1 细胞，从而抑制 T 效应细胞和皮肤炎症。这些发现表明，对于 AD 等炎症性皮肤病来说，这是一种有前景的治疗策略。
The beneficial effects of nonpathogenic bacteria are increasingly being recognized. We reported in a placebo-controlled study with atopic dermatitis (AD) patients that cutaneous exposure to lysates of nonpathogenic bacteria alleviates skin inflammation. To now unravel underlying mechanisms, immune consequences of sensing nonpathogenic bacteriumVitreoscilla filiformislysate (Vf) were characterized analyzing (1) differentiation of dendritic cells (DCs) and, consecutively, (2) effector functions of DCs and T helper (Th) cellsin vitroand in a murine model of AD in NC/Nga micein vivo. Topical treatment with Vf significantly reduced AD-like inflammation in NC/Nga mice. Importantly, cutaneous exposure to Vf in combination with the allergen FITC significantly also reduced subsequent allergen-induced dermatitis indicating active immune modulation. Indeed, innate sensing of Vf predominantly induced IL-10-producing DCs, which was dependent on Toll-like receptor 2 (TLR2) activation. Vf-induced IL-10+ DCs primed naive CD4+ T helper cells to become regulatory IFN-γlowIL-10highTr1 (type 1 regulatory T) cells. These IL-10highTr1 cells were also induced by Vfin vivoand strongly suppressed T effector cells and inflammation. In conclusion, we show that innate sensing of nonpathogenic bacteria by TLR2 induces tolerogenic DCs and regulatory Tr1 cells suppressing T effector cells and cutaneous inflammation. These findings indicate a promising therapeutic strategy for inflammatory skin diseases like AD.