α1β1 integrin is crucial for accumulation of epidermal T cells and the development of psoriasis

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.