title: STAT4: genetics, mechanisms, and implications for autoimmunity.
abstract: Recent advances in genetics and technology have led to breakthroughs in understanding the genes that predispose individuals to autoimmune diseases. A common haplotype of the signal transducer and activator of transcription 4 (STAT4) gene has been shown to be associated with susceptibility to rheumatoid arthritis, systemic lupus erythematosus, and primary Sjögren's syndrome. STAT4 is a transcription factor that transduces interleukin-12, interleukin-23, and type 1 interferon cytokine signals in T cells and monocytes, leading to T-helper type 1 and T-helper type 17 differentiation, monocyte activation, and interferon-gamma production. Although the evidence for this association is very strong and well replicated, the exact mechanism by which polymorphisms in this gene lead to disease remains unknown. In concert with the identification of other disease-associated loci, elucidating how the variant form of STAT4 modulates immune function should lead to an improved understanding of the pathophysiology of autoimmunity.
authors.affiliation: National Institute of Arthritis, Musculoskeletal, and Skin Diseases, 9 Memorial Drive, NIH Building 9, Room 1W108, Bethesda, MD 20892, USA.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Korman
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Kastner
authors.forename: Peter K
authors.initials: PK
authors.lastname: Gregersen
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Remmers
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007110:Immunity, Active; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000276:immunology / Q000378:metabolism; D050797:STAT4 Transcription Factor / Q000235:genetics* / Q000378:metabolism*
chemical_list: D050797:STAT4 Transcription Factor; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22