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STAT4: genetics, mechanisms, and implications for autoimmunity Korman BD; Kastner DL; Gregersen PK; Remmers EFCurr Allergy Asthma Rep 2008[Sep]; 8 (5): 398-403Recent 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 Sjogren'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.|Animals[MESH]|Arthritis, Rheumatoid/*genetics/immunology[MESH]|Autoimmune Diseases/*genetics/immunology[MESH]|Autoimmunity/*genetics[MESH]|Genetic Predisposition to Disease[MESH]|Humans[MESH]|Immunity, Active[MESH]|Lupus Erythematosus, Systemic/*genetics/immunology[MESH]|Polymorphism, Single Nucleotide/genetics[MESH]|Protein Tyrosine Phosphatase, Non-Receptor Type 22/immunology/metabolism[MESH]|STAT4 Transcription Factor/*genetics/*metabolism[MESH] |
