α1β1 integrin is crucial for accumulation of epidermal T cells and the development of psoriasis
α1β1 integrin is crucial for accumulation of epidermal T cells and the development of psoriasis
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DOI：
10.1038/nm1605
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发表时间：
2007-07-01
期刊：
影响因子：
82.9
通讯作者：
Nestle, Frank O.
中科院分区：
文献类型：
--
作者：
Conrad, Curdin;Boyman, Onur;Nestle, Frank O.
银屑病是一种常见的T细胞介导的自身免疫性炎症性疾病。我们发现阻断α (1) β(1)整合素（vla1）与胶原蛋白的相互作用可以防止表皮T细胞的积累和银屑病的免疫病理。α (1) β(1)整合素是一种主要的胶原结合表面受体，仅在表皮T细胞中表达，而在真皮T细胞中不表达。α (1) β(1)阳性T细胞表现出效应记忆细胞的特征表面标记，含有高水平的γ干扰素，但不含白细胞介素-4。在临床相关的异种移植模型中，阻断α (1) β(1)可抑制T细胞向表皮的迁移。这与完全抑制牛皮癣的发展是平行的，与肿瘤坏死因子- α阻滞剂引起的效果相当。这些结果确定了α (1) β(1)在控制表皮1型极化效应记忆T细胞积累中的关键作用，并为银屑病治疗的新策略提供了基础，重点是T细胞-细胞外基质相互作用。
Psoriasis is a common T cell-mediated autoimmune inflammatory disease. We show that blocking the interaction of alpha(1)beta(1) integrin (VLA-1) with collagen prevented accumulation of epidermal T cells and immunopathology of psoriasis. alpha(1)beta(1) integrin, a major collagen-binding surface receptor, was exclusively expressed by epidermal but not dermal T cells. alpha(1)beta(1)-positive T cells showed characteristic surface markers of effector memory cells and contained high levels of interferon-gamma but not interleukin-4. Blockade of alpha(1)beta(1) inhibited migration of T cells into the epidermis in a clinically relevant xenotransplantation model. This was paralleled by a complete inhibition of psoriasis development, comparable to that caused by tumor necrosis factor-alpha blockers. These results define a crucial role for alpha(1)beta(1) in controlling the accumulation of epidermal type 1 polarized effector memory T cells in a common human immunopathology and provide the basis for new strategies in psoriasis treatment focusing on T cell-extracellular matrix interactions.