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

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 Creemers and John J. O’Shea
Additional contact information
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

Nature, 2008, vol. 455, issue 7210, 246-250

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.

Date: 2008
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DOI: 10.1038/nature07210

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