Environmentally responsive and reversible regulation of epidermal barrier function by γδ T cells
Environmentally responsive and reversible regulation of epidermal barrier function by γδ T cells
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DOI：
10.1038/sj.jid.5700120
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发表时间：
2006-04-01
影响因子：
6.5
通讯作者：
Tigelaar, Robert E.
中科院分区：
文献类型：
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作者：
Girardi, Michael;Lewis, Julia M.;Tigelaar, Robert E.
上皮内淋巴细胞（IEL）网络可能构成体内最大的T细胞区室，但对其了解甚少。IEL显示出有限的T细胞受体（TCR）多样性，并且已被提出响应于一般的应激信号而不是病原体特异性抗原。与此一致，皮肤驻留TCR γ δ（+）细胞，称为树突状表皮T细胞（DETC），下调皮肤炎症，促进伤口愈合，并防止皮肤肿瘤形成。这些多效性效应共同表明，DETC（和IEL更普遍）可能有助于上皮维护和屏障功能。目前的研究验证了这一假设。使用皮肤表面阻抗分析来测量水合状态和经表皮水分损失，我们表明，表皮屏障是有缺陷的γ δ T细胞缺陷小鼠。然而，这并不代表γ δ细胞的组成性作用，而是依赖于环境挑战的作用，这与淋巴细胞的主要作用是宿主对其环境的反应一致。同样，通过显示V γ 5（+）胎儿胸腺细胞重建TCR δ（-/-）小鼠中的屏障功能缺陷，而V γ 5（-/-）小鼠也显示皮肤生理学中的环境响应缺陷，证明了生理性DETC相关TCR的重要性。
The intraepithelial lymphocyte (IEL) network possibly composes the largest T-cell compartment in the body, but it is poorly understood. IELs show limited T-cell receptor (TCR) diversity and have been proposed to respond to generic stress signals rather than pathogen-specific antigens. Consistent with this, skin-resident TCR gamma delta(+) cells, known as dendritic epidermal T cells (DETC), downregulate cutaneous inflammation, promote wound healing, and protect against cutaneous neoplasia. These pleiotropic effects collectively suggest that DETC (and IEL more generally) may contribute to epithelial maintenance and barrier function. The present studies test this hypothesis. Using skin surface impedance analysis to measure hydration status and transepidermal water loss, we show that the epidermal barrier is defective in gamma delta T-cell deficient mice. However, this does not represent a constitutive role of gamma delta cells, but rather one that is dependent on environmental challenge, consistent with the primary role for lymphocytes being the response of the host to its environment. Likewise, the importance of the physiologic DETC-associated TCR is demonstrated by showing that V gamma 5(+) fetal thymocytes reconstitute the barrier function defect in TCR delta(-/-) mice, while V gamma 5(-/-) mice also show environmentally responsive defects in cutaneous physiology.