A postmigrational switch among skin-derived dendritic cells to a macrophage-like phenotype is predetermined by the intracutaneous cytokine balance
A postmigrational switch among skin-derived dendritic cells to a macrophage-like phenotype is predetermined by the intracutaneous cytokine balance
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DOI：
10.4049/jimmunol.176.12.7232
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发表时间：
2006-06-15
影响因子：
4.4
通讯作者：
Pinedo, HM
中科院分区：
文献类型：
--
作者：
de Gruijl, TD;Sombroek, CC;Pinedo, HM
树突状细胞（DC）迁移到次级淋巴器官的促炎条件下，符合其成熟和收购的T细胞刺激能力。相反，受损的DC激活，例如，在肿瘤条件环境中，可能阻碍它们的活化，并可能阻碍它们随后迁移到淋巴结，分别导致免疫耐受或免疫忽视。在这项研究中，在外周皮肤微环境中的细胞因子对迁移的皮肤DC的活化状态的影响进行了评估，使用离体人皮肤外植体模型。我们观察到从非条件皮肤迁移后7天内，从成熟的CD 83（+）DC向未成熟的CD 14（+）巨噬细胞样细胞的表型转变。这些巨噬细胞样细胞显示出较差的T细胞刺激能力，并且缺乏CCR 7的表达，从而阻止了它们迁移到淋巴结中的副皮质T细胞区域。在迁移启动过程中，抑制性和刺激性细胞因子的平衡决定了DC的迁移后命运，IL-10加速了DC的表型转换，而GM-CSF和IL-4阻止了DC的表型转换，一旦建立，这种转换就被证明是不可逆的。这些观察结果表明，在免疫抑制的环境中，移行后DC-巨噬细胞转移可能会阻碍T细胞活化，但也可以通过GM-CSF和/或IL-4预先调节组织微环境来预防。
Migration of dendritic cells (DC) to secondary lymphoid organs under proinflammatory conditions coincides with their maturation and acquisition of T cell stimulatory abilities. In contrast, impaired activation of DC, e.g., in tumor-conditioned environments, may hamper their activation and possibly their subsequent migration to lymph nodes, leading to either immunological tolerance or ignorance, respectively. In this study, the influence of cytokines in the peripheral skin microenvironment on the activation state of migrating cutaneous DC was assessed using an ex vivo human skin explant model. We observed a phenotypic shift from mature CD83(+) DC to immature CD14(+) macrophage-like cells within 7 days subsequent to migration from unconditioned skin. These macrophage-like cells displayed a poor T cell stimulatory ability and lacked expression of CCR7, thus precluding their migration to paracortical T cell areas in the lymph nodes. The balance of suppressive and stimulatory cytokines during the initiation of migration decided the postmigrational fate of DC with IL-10 accelerating and GM-CSF and IL-4 preventing the phenotypic switch, which proved irreversible once established. These observations indicate that, in immunosuppressed environments, a postmigrational DC-to-macrophage shift may hinder T cell activation, but also that it may be prevented by prior conditioning of the tissue microenvironment by GM-CSF and/or IL-4.