Identification of a novel population of Langerin+ dendritic cells.

Identification of a novel population of Langerin+ dendritic cells.
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DOI:
10.1084/jem.20071966
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发表时间:
2007-12-24
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Hogquist KA
Hogquist KA
中科院分区:
其他
文献类型:
--
作者:
Bursch LS;Wang L;Igyarto B;Kissenpfennig A;Malissen B;Kaplan DH;Hogquist KA

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朗格汉斯细胞(LCs)是一种抗原呈递细胞,存在于皮肤表皮并转运到淋巴结(LNs)。这些细胞在皮肤免疫反应中的一般作用尚不清楚,因为不同的LC耗尽模型对它们在接触性超敏反应(CHS)反应中的作用得出了相反的结论。在比较这些模型时,我们发现了一种新的LCs种群,它存在于真皮层中,而不像以前认为的那样代表迁移的表皮LCs。与表皮LCs不同,真皮Langerin+树突状细胞(dc)对辐射敏感,并表现出独特的细胞表面表型。真皮Langerin+ dc在炎症后稳定状态下从皮肤向LNs迁移,在皮肤引流LNs中占Langerin+ dc的大多数。Lang-DTREGFP敲入小鼠的表皮和真皮Langerin+ dc均通过白喉毒素处理而减少。相比之下,转基因hLang-DTA小鼠缺乏表皮LCs,但真皮Langerin+ dc数量正常。在表皮和真皮lccs消耗时,CHS反应被取消,但在没有表皮lccs的情况下不受影响。这表明真皮LCs可以介导CHS,并为之前在两种模式系统中观察到的差异提供了解释。
Langerhans cells (LCs) are antigen-presenting cells that reside in the epidermis of the skin and traffic to lymph nodes (LNs). The general role of these cells in skin immune responses is not clear because distinct models of LC depletion resulted in opposite conclusions about their role in contact hypersensitivity (CHS) responses. While comparing these models, we discovered a novel population of LCs that resides in the dermis and does not represent migrating epidermal LCs, as previously thought. Unlike epidermal LCs, dermal Langerin+ dendritic cells (DCs) were radiosensitive and displayed a distinct cell surface phenotype. Dermal Langerin+ DCs migrate from the skin to the LNs after inflammation and in the steady state, and represent the majority of Langerin+ DCs in skin draining LNs. Both epidermal and dermal Langerin+ DCs were depleted by treatment with diphtheria toxin in Lang-DTREGFP knock-in mice. In contrast, transgenic hLang-DTA mice lack epidermal LCs, but have normal numbers of dermal Langerin+ DCs. CHS responses were abrogated upon depletion of both epidermal and dermal LCs, but were unaffected in the absence of only epidermal LCs. This suggests that dermal LCs can mediate CHS and provides an explanation for previous differences observed in the two-model systems.
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