title: Signal transducer and activator of transcription 3: a year in review.
abstract: OBJECTIVE
  Signal transducer and activator of transcription 3 (STAT3) is an important transcription factor involved in a wide variety of cellular functions. Germline loss-of-function mutations are known to cause hyper-IgE immunodeficiency (autosomal dominant hyper IgE syndrome), whereas somatic gain-of-function mutations have been described in large granular cell leukemia, and polymorphisms in STAT3 have been associated with inflammatory bowel disease and other solid organ tumors. The review examines recent discoveries in our understanding of the nonmalignant disease processes affected by STAT3 mutations in human disease.
  
  
  RESULTS
  Germline STAT3 gain-of-function mutations have recently been identified in patients with an early-onset autoimmunity/lymphoproliferative syndrome. STAT3 plays a previously unrecognized role in several facets of the pathogenesis of allergy. Loss-of-function STAT3 mutations revealed critical roles for STAT3 in the development and function of several lymphocyte populations and in their role in host defense.
  
  
  CONCLUSIONS
  The discovery of new gain-of-function mutations in STAT3, as well as new studies among patients with loss-of-function mutations, expand the understanding of the pathophysiology of STAT3 function and its importance in regulating the immune system. These findings contribute to elucidating STAT3 biology and clinical symptoms in patients with the different disease phenotypes.
authors.affiliation: aSection of Immunology, Department of Pediatrics, Allergy and Rheumatology, Baylor College of Medicine, Texas Children's Hospital Center for Human Immunobiology, Houston, Texas bNational Institutes of Health, Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases, NIAID, Bethesda, Maryland, USA cDepartment of Pediatrics and Department of Microbiology, Immunology and Infectiology, University of Montreal, CHU Sainte-Justine Research Centre, Montreal, Quebec, Canada *Josh Milner and Elie Haddad share the senior authorship to the writing of this article.
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Forbes
authors.forename: Josh
authors.initials: J
authors.lastname: Milner
authors.forename: Elie
authors.initials: E
authors.lastname: Haddad
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D015551:Autoimmunity; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007156:Immunologic Memory; D007239:Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000821:virology; D020381:Interleukin-17 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009154:Mutation; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D020381:Interleukin-17; D050796:STAT3 Transcription Factor