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Nat Med. 2007 Jul;13(7):836-42. Epub 2007 Jul 1.

Alpha1beta1 integrin is crucial for accumulation of epidermal T cells and the development of psoriasis.

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1
Department of Dermatology, University Hospital of Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland. curdin.conrad@usz.ch

Abstract

Psoriasis is a common T cell-mediated autoimmune inflammatory disease. We show that blocking the interaction of alpha1beta1 integrin (VLA-1) with collagen prevented accumulation of epidermal T cells and immunopathology of psoriasis. Alpha1beta1 integrin, a major collagen-binding surface receptor, was exclusively expressed by epidermal but not dermal T cells. Alpha1beta1-positive T cells showed characteristic surface markers of effector memory cells and contained high levels of interferon-gamma but not interleukin-4. Blockade of alpha1beta1 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 alpha1beta1 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.

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PMID:
17603494
DOI:
10.1038/nm1605
[Indexed for MEDLINE]

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