title: Jak3, severe combined immunodeficiency, and a new class of immunosuppressive drugs.
abstract: 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.
authors.affiliation: Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892-1820, USA.
authors.forename: Marko
authors.initials: M
authors.lastname: Pesu
authors.forename: Fabio
authors.initials: F
authors.lastname: Candotti
authors.forename: Matthew
authors.initials: M
authors.lastname: Husa
authors.forename: Sigrun R
authors.initials: SR
authors.lastname: Hofmann
authors.forename: Luigi D
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Shea
mesh_terms: D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D053616:Janus Kinase 3; D009154:Mutation / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology*; D018121:Receptors, Cytokine / Q000235:genetics*; D016511:Severe Combined Immunodeficiency / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction
chemical_list: D007166:Immunosuppressive Agents; D018121:Receptors, Cytokine; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3