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T-cell-expressed proprotein convertase furin is essential for maintenance of peripheral immune tolerance

Author

Listed:
  • Marko Pesu

    (Molecular Immunology and Inflammation Branch, National Institute for Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Wendy T. Watford

    (Molecular Immunology and Inflammation Branch, National Institute for Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Lai Wei

    (Molecular Immunology and Inflammation Branch, National Institute for Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Lili Xu

    (Mucosal Immunity Section, Laboratory of Host Defenses,)

  • Ivan Fuss

    (Mucosal Immunity Section, Laboratory of Host Defenses,)

  • Warren Strober

    (Mucosal Immunity Section, Laboratory of Host Defenses,)

  • John Andersson

    (Cellular Immunology Section, Laboratory of Immunology)

  • Ethan M. Shevach

    (Cellular Immunology Section, Laboratory of Immunology)

  • Martha Quezado

    (Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Nicolas Bouladoux

    (Mucosal Immunology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Anton Roebroek

    (Experimental Mouse Genetics,)

  • Yasmine Belkaid

    (Mucosal Immunology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • John Creemers

    (Laboratory for Biochemical Neuroendocrinology, K.U. Leuven and V.I.B., B-3000 Leuven, Belgium)

  • John J. O’Shea

    (Molecular Immunology and Inflammation Branch, National Institute for Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

Abstract

Furin's role in T cells The protease furin is induced on T cell activation and is a target of Stat-transcription factors in T cells. Studying furin has been hampered by the fact that germline deletion of this gene is embryonically lethal. Here furin's physiological role in T cells is studied using a T cell-specific furin knockout mice. The striking finding is that conditional deletion of furin in T cells results in loss of peripheral tolerance and systemic autoimmune disease. Furin deficiency compromises TGF-β release and Treg function, and is associated with inherently more aggressive effector T cells. This research suggests that inhibiting furin may promote the immune response but may also cause the loss of peripheral tolerance by reducing levels of bioavailable TGF-β-1.

Suggested Citation

  • Marko Pesu & Wendy T. Watford & Lai Wei & Lili Xu & Ivan Fuss & Warren Strober & John Andersson & Ethan M. Shevach & Martha Quezado & Nicolas Bouladoux & Anton Roebroek & Yasmine Belkaid & John Creeme, 2008. "T-cell-expressed proprotein convertase furin is essential for maintenance of peripheral immune tolerance," Nature, Nature, vol. 455(7210), pages 246-250, September.
    • Handle: RePEc:nat:nature:v:455:y:2008:i:7210:d:10.1038_nature07210
    DOI: 10.1038/nature07210
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