Article | Published:

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

Nature Medicine volume 13, pages 836842 (2007) | Download Citation

Abstract

Psoriasis is a common T cell–mediated autoimmune inflammatory disease. We show that blocking the interaction of α1β1 integrin (VLA-1) with collagen prevented accumulation of epidermal T cells and immunopathology of psoriasis. α1β1 integrin, a major collagen-binding surface receptor, was exclusively expressed by epidermal but not dermal T cells. α1β1-positive T cells showed characteristic surface markers of effector memory cells and contained high levels of interferon-γ but not interleukin-4. Blockade of α1β1 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-α blockers. These results define a crucial role for α1β1 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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Acknowledgements

We thank B.J. Nickoloff, M. Gilliet, K.S. Lang and P. Johansen for discussions. We appreciate the excellent technical assistance by C. Dudli and A. Perez. We would further like to thank T. Baechi for help with confocal microscopy. This work was supported by the Swiss National Science Foundation, Biogen-Idec, the Bonizzi-Theler-Foundation and the Wellcome Trust. The authors acknowledge financial support from the UK Department of Health through the National Institute for Health Research Biomedical Research Centre award to Guy's & St Thomas' National Health Service Foundation Trust in partnership with King's College London.

Author information

Author notes

    • Onur Boyman

    Present address: Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland.

    • Onur Boyman
    •  & Giulia Tonel

    These authors contributed equally to this work.

Affiliations

  1. Department of Dermatology, University Hospital of Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland.

    • Curdin Conrad
    • , Onur Boyman
    • , Giulia Tonel
    •  & Adrian Tun-Kyi
  2. St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, King's College London School of Medicine, Floor 8 Guy's Tower, Guy's Hospital, St. Thomas' Street, London, SE19RT, UK.

    • Giulia Tonel
    • , Ute Laggner
    •  & Frank O Nestle
  3. Biogen Idec Inc., 14 Cambridge Center, Cambridge, Massachusetts 02142, USA.

    • Antonin de Fougerolles
    • , Victor Kotelianski
    •  & Humphrey Gardner

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Contributions

C.C., O.B. and G.T. performed mouse, cell culture and molecular biology experiments and data analysis. A.T.-K. performed PCR experiments and data analysis. U.L. performed flow cytometry, culture of cell lines and clones and data analysis. A.d.F., V.K. and H.G. provided expertise, reagents and input into manuscript preparation. Experimental design, data analysis and manuscript preparation were carried out by C.C. and F.O.N. All authors read and commented on the paper.

Competing interests

A.d.F., V.K. and H.G. are former employees of Biogen Idec.

F.O.N. has been consulting for and received lecturing fees from Biogen Idec.

The study has received scientific grant support from Biogen Idec.

Corresponding authors

Correspondence to Curdin Conrad or Frank O Nestle.

Supplementary information

PDF files

  1. 1.

    Supplementary Fig. 1

    CD3+/CD8+ and CD3+/CD4+ epidermal T cells express α1 integrin.

  2. 2.

    Supplementary Fig. 2

    Extended phenotype of freshly isolated α1β1+ psoriatic T cells.

  3. 3.

    Supplementary Fig. 3

    Extended phenotype of α1β1 expressing psoriatic T cell lines.

  4. 4.

    Supplementary Fig. 4

    Extended phenotype of α1β1 expressing psoriatic T cell clones.

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    Supplementary Fig. 5

    Efficacy of α1β1 blockade in treatment of established psoriatic skin.

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    Supplementary Fig. 6

    No induction of apoptosis via monoclonal antibody to α1.

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    Supplementary Fig. 7

    Migration of T cells through collagen type IV increases α1β1-expression on T cells in vitro.

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DOI

https://doi.org/10.1038/nm1605

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