The Mandatory Role of IL-10-Producing and OX40 Ligand-Expressing Mature Langerhans Cells in Local UVB-Induced Immunosuppression
The Mandatory Role of IL-10-Producing and OX40 Ligand-Expressing Mature Langerhans Cells in Local UVB-Induced Immunosuppression
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DOI：
10.4049/jimmunol.0903254
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发表时间：
2010-05-15
影响因子：
4.4
通讯作者：
Tokura, Yoshiki
中科院分区：
文献类型：
--
作者：
Yoshiki, Ryutaro;Kabashima, Kenji;Tokura, Yoshiki
UVB诱导的局部免疫抑制的机制是光免疫学中有待阐明的中心问题。已经报道了相当数量的细胞和因子参与致敏相依赖性抑制，包括朗格汉斯细胞（LC）、调节性T细胞、IL-10和TNF-α。最近的重要发现，LC-耗竭小鼠，而表现出增强的接触性超敏反应，促使我们重新评估的作用，LC沿着与真皮树突状细胞（dDC）的UVB诱导的免疫抑制的机制。我们研究了来自UVB照射（300 ml/cm（2））的BALB/c小鼠皮肤的LC和dDC中OX 40配体（OX 40 L）的表面表达和IL-10的细胞内表达，以及来自UVB照射的半抗原涂抹小鼠的迁移到区域淋巴结的LC和dDC。在从UVB照射的皮肤制备的表皮和真皮细胞悬液中，LC表达OX 40 L以及CD 86，并以高于Langerin（-）dDC的水平产生IL-10。UVB诱导的免疫抑制通过施用IL-10中和或OX 40 L阻断Ab而减弱。在应用半抗原后1天解剖UVB照射的、涂有半抗原的皮肤的小鼠中，接触性超敏反应恢复，因为这种治疗允许dDC而不是LC迁移到引流淋巴结。此外，LC耗尽小鼠使用朗格林白喉毒素受体敲入小鼠表现出受损的UVB诱导的免疫抑制。这些结果表明，在UVB暴露的皮肤中，IL-10产生和OX 40 L表达的LC对于Ag特异性调节性T细胞的诱导是强制性的。免疫学杂志，2010，184：5670-5677。
The mechanism underlying the local UVB-induced immunosuppression is a central issue to be clarified in photoimmunology. There have been reported a considerable number of cells and factors that participate in the sensitization phase-dependent suppression, including Langerhans cells (LCs), regulatory T cells, IL-10, and TNF-alpha. The recent important finding that LC-depleted mice rather exhibit enhanced contact hypersensitivity responses urged us to re-evaluate the role of LCs along with dermal dendritic cells (dDCs) in the mechanism of UVB-induced immunosuppression. We studied the surface expression of OX40 ligand (OX40L) and the intracellular expression of IL-10 in LCs and dDCs from UVB-irradiated (300 ml/cm(2)) skin of BALB/c mice and those migrating to the regional lymph nodes from UVB-irradiated, hapten-painted mice. In epidermal and dermal cell suspensions prepared from the UVB-irradiated skin, LCs expressed OX40L as well as CD86 and produced IL-10 at a higher level than Langerin(-) dDCs. The UVB-induced immunosuppression was attenuated by the administration of IL-10 neutralizing or OX40L-blocking Abs. In mice whose UVB-irradiated, hapten-painted skin was dissected 1 d after hapten application, the contact hypersensitivity response was restored, because this treatment allowed dDCs but not LCs to migrate to the draining lymph nodes. Moreover, LC-depleted mice by using Langerin-diphtheria toxin receptor knocked-in mice showed impaired UVB-induced immunosuppression. These results suggest that IL-10 producing and OX40L-expressing LCs in the UVB-exposed skin are mandatory for the induction of Ag-specific regulatory T cells. The Journal of Immunology, 2010, 184: 5670-5677.