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Jak3, severe combined immunodeficiency, and a new class of immunosuppressive drugs

Authors

  • Marko Pesu,

    1. Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, USA.
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  • Fabio Candotti,

    1. Genetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, MD, USA.
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  • Matthew Husa,

    1. Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, USA.
    2. Howard Hughes-NIH Scholars Program National Institutes of Health, Bethesda, MD, USA.
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  • Sigrun R. Hofmann,

    1. Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, USA.
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  • Luigi D. Notarangelo,

    1. Institute of Molecular Medicine ‘Angelo Nocivelli’, Department of Pediatrics, University of Brescia, Brescia, Italy.
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  • John J. O'Shea

    Corresponding author
    1. Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, USA.
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* John J. O'Shea
Molecular Immunology and Inflammation Branch
National Institute of Arthritis and Musculoskeletal Diseases
Building 10, Room 9N252
Bethesda, MD 20892-1820, USA
Tel.: +1 301 496 2541
Fax: +1 301 402 0012
E-mail: osheajo@mail.nih.gov

Abstract

Summary:  The recent elucidation of the multiple molecular mechanisms underlying severe combined immunodeficiency (SCID) is an impressive example of the power of molecular medicine. Analysis of patients and the concomitant generation of animal models mimicking these disorders have quickly provided great insights into the pathophysiology of these potentially devastating illnesses. In this review, we summarize the discoveries that led to the understanding of the role of cytokine receptors and a specific tyrosine kinase, Janus kinase 3 (Jak3), in the pathogenesis of SCID. We discuss how the identification of mutations of Jak3 in autosomal recessive SCID has facilitated the diagnosis of these disorders, offered new insights into the biology of this kinase, permitted new avenues for therapy, and provided the rationale for a generation of a new class of immunosuppressants.

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