Differential Capability of Human Cutaneous Dendritic Cell Subsets to Initiate Th17 Responses
Differential Capability of Human Cutaneous Dendritic Cell Subsets to Initiate Th17 Responses
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DOI：
10.4049/jimmunol.182.2.921
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发表时间：
2009-01-15
影响因子：
4.4
通讯作者：
Larregina, Adriana T.
中科院分区：
文献类型：
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作者：
Mathers, Alicia R.;Janelsins, Brian M.;Larregina, Adriana T.
人皮肤游走树突状细胞(DC)具有启动和偏向Th1和Th2 CD4(+)T淋巴细胞的能力。然而，人类皮肤树突状细胞是否能够启动促炎Th17反应仍未确定。我们报道，皮肤迁移性DC刺激同种异体幼稚的CD4(+)T细胞，同时分化为两个不同的效应Th17和Th1群体，能够归巢到皮肤，在那里他们会引起严重的皮肤损伤。皮肤迁移性朗格汉斯细胞(SmiLCs)是诱导Th17应答的主要皮肤DC亚群，依赖于IL-15和稳定的IL-6的共同作用，导致初始的CD4(+)T细胞的IL-6反式信号传导。与smiLC不同，纯化的皮肤移行真皮DC不能合成IL-15，也不能偏向Th17应答。然而，这些真皮DC能够在添加IL-15和稳定的IL-6的混合白细胞培养中分化为Th17细胞。总体而言，我们的数据表明，人类表皮smiLCs诱导Th17反应的机制不同于之前描述的机制，并强调了根据这些变化进行临床治疗的必要性。免疫学杂志，2009,182：921-933。
Human skin-migratory dendritic cells (DCs) have the ability to prime and bias Th1 and Th2 CD4(+) T lymphocytes. However, whether human cutaneous DCs are capable of initiating proinflammatory Th17 responses remains undetermined. We report that skin-migratory DCs stimulate allogeneic naive CD4(+) T cells that differentiate simultaneously into two distinct effector Th17 and Thl populations capable of homing to the skin, where they induce severe cutaneous damage. Skin-migratory Langerhans cells (smiLCs) were the main cutaneous DC subset capable of inducing Th17 responses dependent on the combined effects of IL-15 and stabilized IL-6, which resulted in IL-6 trans-signaling of naive CD4(+) T cells. Different from smiLCs, purified skin-migratory dermal DCs did not synthesize IL-15 and were unable to bias Th17 responses. Nevertheless, these dermal DCs were capable of differentiating Th17 cells in mixed leukocyte cultures supplemented with IL-15 and stabilized IL-6. Overall, our data demonstrate that human epidermal smiLCs induce Th17 responses by mechanisms different from those previously described and highlight the need to target clinical treatments based on these variations. The Journal of Immunology, 2009, 182: 921-933.