Embryonic trafficking of γδ T cells to skin is dependent on E/P selectin ligands and CCR4
Embryonic trafficking of γδ T cells to skin is dependent on E/P selectin ligands and CCR4
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DOI：
10.1073/pnas.0912943107
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发表时间：
2010-04-20
影响因子：
11.1
通讯作者：
Kupper, Thomas S.
中科院分区：
文献类型：
--
作者：
Jiang, Xiaodong;Campbell, James J.;Kupper, Thomas S.
树突状表皮T细胞（Dendritic epidermal T cells， DETC）表达不变的V γ 3/V δ 1 T细胞受体，出现在胎儿表皮中，并形成常驻表皮T细胞群。它们在胸腺中的时间发育已被广泛研究。然而，关于DETC从胸腺到表皮的胚胎运输的机制知之甚少。我们证明成人皮肤中的DETC以及胎儿胸腺中的DETC前体表达E和P选择素配体（E-和P- light）。缺乏α 1,3聚焦转移酶IV和VII （FTIV/VII）的小鼠不能合成形成这些选择素配体关键元素的碳水化合物基序。与正常小鼠相比，FTIV/VII-/-小鼠表皮中DETC的数量明显减少。然而，在正常小鼠和FTIV/VII-/-小鼠中，胎儿胸腺中DETC前体的发育是相同的，这表明FTIV/VII-/-小鼠中产生的DETC前体由于缺乏E-和p -光而不能有效地运输到皮肤。我们通过每天向怀孕小鼠注射E和P选择素的阻断抗体来验证这一假设。用抗选择素抗体处理过的母鼠所生的小鼠，而用同型对照处理过的母鼠所生的小鼠，DETC的数量显著减少。为了测试趋化因子受体在DETC皮肤归巢中的作用，我们分别检测了CCR4（-/-）和CCR10（-/-）小鼠的皮肤。在CCR4（-/-）小鼠中，DETC显著降低，而在CCR10（-/-）小鼠中，DETC处于正常水平。我们的研究结果为DETC前体向皮肤的胚胎迁移中运输分子的关键作用提供了证据。
Dendritic epidermal T cells (DETC) express an invariant V gamma 3/V delta 1 T-cell receptor, appear in fetal epidermis, and forma population of resident epidermal T cells. Their temporal development in the thymus has been studied extensively. However, little is known about the mechanisms involved in the embryonic trafficking of DETC from thymus to epidermis. We demonstrate that DETC in adult skin, as well as the DETC precursors in fetal thymus, express E and P selectin ligands (E- and P-lig). Mice deficient in alpha 1,3 fucosyltransferases IV and VII (FTIV/VII) cannot synthesize the carbohydrate motifs that form key elements of these selectin ligands. The numbers of DETC in the epidermis of FTIV/VII-/- mice were dramatically reduced compared with normal mice. However, the development of DETC precursors in fetal thymus was identical in normal and FTIV/VII-/- mice, suggesting that the DETC precursors produced in FTIV/VII-/- mice could not traffic effectively to skin because they lack E- and P-lig. We tested this hypothesis by daily injection of blocking antibodies against E and P selectin into pregnant mice. Mice born from dams treated with anti-selectin antibodies, but not those born from dams treated with isotype control, had significantly diminished numbers of DETC. To test the role of chemokine receptors in DETC skin homing, we examined skin from CCR4(-/-) and CCR10(-/-) mice, respectively. DETC were significantly reduced in CCR4(-/-) mice but were present at normal levels in CCR10(-/-) mice. Our results present evidence for the crucial role of trafficking molecules in embryonic migration of DETC precursors to skin.