Alpha1beta1 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 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.
Conrad
Curdin
C
Department of Dermatology, University Hospital of Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland. curdin.conrad@usz.ch
Boyman
Onur
O
Tonel
Giulia
G
Tun-Kyi
Adrian
A
Laggner
Ute
U
de Fougerolles
Antonin
A
Kotelianski
Victor
V
Gardner
Humphrey
H
Nestle
Frank O
FO
D000818:Animals; D000911:Antibodies, Monoclonal; D000078404:Epidermal Cells; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006801:Humans; D039222:Integrin alpha1beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D011565:Psoriasis / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D039222:Integrin alpha1beta1