JAK and STAT Signaling Molecules in Immunoregulation and Immune-Mediated Disease

• Published in: Immunity (Cambridge, Mass.) Vol. 36; no. 4; pp. 542 - 550
• Main Authors: O'Shea, John J., Plenge, Robert
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20-04-2012; Elsevier Limited
• Subjects: Autoimmune Diseases - genetics; Autoimmune Diseases - metabolism; Autoimmune Diseases - therapy; Autoimmunity; Competition; Cytokines; Cytokines - immunology; Cytokines - metabolism; Gene expression; Gene Expression Regulation; Gene loci; Growth hormones; Humans; Immune system; Immunity, Innate; Interferons - immunology; Interferons - metabolism; Janus Kinases - antagonists & inhibitors; Janus Kinases - immunology; Janus Kinases - metabolism; Kinases; Rodents; Signal Transduction; STAT Transcription Factors - immunology; STAT Transcription Factors - metabolism
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2012.03.014

The discovery of the Janus kinase (JAK)-signal transducer and activator of transcripton (STAT) signaling pathway, a landmark in cell biology, provided a simple mechanism for gene regulation that dramatically advanced our understanding of the action of hormones, interferons, colony-stimulating factors, and interleukins. As we learn more about the complexities of immune responses, new insights into the functions of this pathway continue to be revealed, aided by technology that permits genome-wide views. As we celebrate the 20th anniversary of the discovery of this paradigm in cell signaling, it is particularly edifying to see how this knowledge has rapidly been translated to human immune disease. Not only have genome-wide association studies demonstrated that this pathway is highly relevant to human autoimmunity, but targeting JAKs is now a reality in immune-mediated disease.