STAT3

About STAT3

STAT3 Signal Transducer and Activator of Transcription 3 on chromosome 17q21.2 encodes a transcription factor activated by Janus kinases downstream of receptors for IL 6 family cytokines, IL 10, IL 21, IL 23, and many growth factors. Once phosphorylated, STAT3 forms dimers that enter the nucleus and regulate genes involved in inflammation, immunity, cell growth, and survival. Germline dominant negative STAT3 variants cause autosomal dominant hyper IgE syndrome, also called Job syndrome, identified as its cause in 2007. Features include eczema, recurrent staphylococcal skin abscesses that are often cold, without typical warmth and redness, pneumonias complicated by lung cysts called pneumatoceles, mucocutaneous candidiasis, characteristic facial features, retained primary teeth, minor trauma fractures, scoliosis, and arterial aneurysms, together with very high serum IgE and eosinophilia. Impaired development of Th17 cells explains much of the susceptibility to staphylococcal and candida infections. Germline gain of function STAT3 variants cause a different disorder with early onset multiorgan autoimmunity and lymphoproliferation. Somatic activating STAT3 mutations are common in T cell large granular lymphocytic leukemia and occur in inflammatory hepatocellular adenomas and other tumors. JAK inhibitors are used in some STAT3 related inflammatory diseases.