Abstract
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.