title: STAT3 is a central regulator of lymphocyte differentiation and function.
abstract: Signalling in lymphocytes through cytokine receptors is critical for their development, activation and differentiation into effector cells that mediate protection against pathogens and provide the host with protective immunological memory. The essential role of cytokine signalling has been established not only by the generation and examination of gene-targeted mice, but also 'Experiments of Nature' whereby monogenic mutations cause primary immunodeficient conditions characterised by impaired immunity to infectious diseases due to compromised lymphocyte function. Mutations in STAT3 cause autosomal dominant hyper-IgE syndrome. Here, we will review how the study of STAT3-deficient individuals has revealed non-redundant functions of STAT3 and specific cytokines in human lymphocyte biology, and have delineated mechanisms underlying the distinct clinical features of autosomal dominant hyper-IgE syndrome.
authors.affiliation: Immunology and Immunodeficiency Group, Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; St Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW, Australia.
authors.forename: Alisa
authors.initials: A
authors.lastname: Kane
authors.affiliation: Immunology and Immunodeficiency Group, Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; St Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW, Australia.
authors.forename: Elissa K
authors.initials: EK
authors.lastname: Deenick
authors.affiliation: Immunology and Immunodeficiency Group, Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; St Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW, Australia.
authors.forename: Cindy S
authors.initials: CS
authors.lastname: Ma
authors.affiliation: John Curtin School of Medical Research, Australian National University, ACT, Australia; Department of Immunology, The Canberra Hospital, ACT, Australia.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Cook
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Gulbu
authors.initials: G
authors.lastname: Uzel
authors.affiliation: Immunology and Immunodeficiency Group, Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; St Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW, Australia. Electronic address: s.tangye@garvan.org.au.
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Tangye
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D006801:Humans; D007589:Job Syndrome / Q000276:immunology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D050796:STAT3 Transcription Factor / Q000276:immunology*
chemical_list: D050796:STAT3 Transcription Factor