Macrophage inflammatory protein 3alpha is involved in the constitutive trafficking of epidermal langerhans cells.
Macrophage inflammatory protein 3alpha is involved in the constitutive trafficking of epidermal langerhans cells.
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DOI：
10.1084/jem.190.12.1755
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发表时间：
1999-12-20
期刊：
影响因子：
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通讯作者：
Maurer D
中科院分区：
文献类型：
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作者：
Charbonnier AS;Kohrgruber N;Kriehuber E;Stingl G;Rot A;Maurer D
某些类型的树突状细胞 (DC) 出现在各种病因的炎症病变中，而其他 DC，例如朗格汉斯细胞 (LC)，则组成性地分布在外周器官中。到目前为止，这种差异行为背后的分子机制尚未阐明。在这里，我们表明 CD1a+ LC 前体选择性且特异性地响应 CC 趋化因子巨噬细胞炎症蛋白 (MIP)-3α。相反，DC 和单核细胞的 CD14+ 前体不会被 MIP-3α 吸引。 LC 在成熟过程中失去了对 MIP-3α 的迁移反应性，非 LC DC 不会获得 MIP-3α 敏感性。以下观察结果进一步支持了 MIP-3α 可能负责选择性 LC 募集至表皮的观点： (a) MIP-3α 由临床正常人类皮肤中的角质形成细胞和小静脉内皮细胞表达； (b) LC 表达 CC 趋化因子受体 (CCR)6，这是原位和体外唯一的 MIP-3α 受体； (c) 正常表皮中未发现的非 LC DC 缺乏 CCR6。成熟形式的 LC 和非 LC DC 对 MIP-3β（一种 CCR7 配体）表现出相当的敏感性，表明 DC 亚型特异性趋化因子反应仅限于定型前体阶段。尽管 LC 前体主要表达 CCR6，但非 LC DC 前体表现出广泛的趋化因子受体库。这些发现反映了一种情况，即两个不同 DC 亚群趋化因子受体的差异表达决定了它们的功能行为。一种类型，即 LC，对 MIP-3α 做出反应并进入皮肤以组成性筛选表皮，而另一种类型，即“炎症”DC，则响应于多种不同的趋化因子而迁移，并参与炎症组织反应的放大和调节。
Certain types of dendritic cells (DCs) appear in inflammatory lesions of various etiologies, whereas other DCs, e.g., Langerhans cells (LCs), populate peripheral organs constitutively. Until now, the molecular mechanism behind such differential behavior has not been elucidated. Here, we show that CD1a+ LC precursors respond selectively and specifically to the CC chemokine macrophage inflammatory protein (MIP)-3α. In contrast, CD14+ precursors of DC and monocytes are not attracted by MIP-3α. LCs lose the migratory responsiveness to MIP-3α during their maturation, and non-LC DCs do not acquire MIP-3α sensitivity. The notion that MIP-3α may be responsible for selective LC recruitment into the epidermis is further supported by the following observations: (a) MIP-3α is expressed by keratinocytes and venular endothelial cells in clinically normal appearing human skin; (b) LCs express CC chemokine receptor (CCR)6, the sole MIP-3α receptor both in situ and in vitro; and (c) non-LC DCs that are not found in normal epidermis lack CCR6. The mature forms of LCs and non-LC DCs display comparable sensitivity for MIP-3β, a CCR7 ligand, suggesting that DC subtype–specific chemokine responses are restricted to the committed precursor stage. Although LC precursors express primarily CCR6, non-LC DC precursors display a broad chemokine receptor repertoire. These findings reflect a scenario where the differential expression of chemokine receptors by two different subpopulations of DCs determines their functional behavior. One type, the LC, responds to MIP-3α and enters skin to screen the epidermis constitutively, whereas the other type, the “inflammatory” DC, migrates in response to a wide array of different chemokines and is involved in the amplification and modulation of the inflammatory tissue response.