2. Academic Validation
  3. JAK-STAT signaling in human disease: From genetic syndromes to clinical inhibition

JAK-STAT signaling in human disease: From genetic syndromes to clinical inhibition

  • J Allergy Clin Immunol. 2021 Oct;148(4):911-925. doi: 10.1016/j.jaci.2021.08.004.
Yiming Luo 1,  Madison Alexander 2,  Massimo Gadina 3,  John J O'Shea 4,  Francoise Meylan 3,  Daniella M Schwartz 5
Affiliations

Affiliations

  • 1 Vasculitis Translational Research Program, Systemic Autoimmunity Branch, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, Bethesda, Md.
  • 2 Translational Immunology Section, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, Bethesda, Md.
  • 3 Office of Science and Technology, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, Bethesda, Md.
  • 4 Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, Bethesda, Md.
  • 5 Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md. Electronic address: [email protected].
PMID: 34625141 DOI: 10.1016/j.jaci.2021.08.004
Abstract

Since its discovery, the Janus kinase-signal transduction and activation of transcription (JAK-STAT) pathway has become recognized as a central mediator of widespread and varied human physiological processes. The field of JAK-STAT biology, particularly its clinical relevance, continues to be shaped by 2 important advances. First, the increased use of genomic Sequencing has led to the discovery of novel clinical syndromes caused by mutations in JAK and STAT genes. This has provided insights regarding the consequences of aberrant JAK-STAT signaling for immunity, lymphoproliferation, and malignancy. In addition, since the approval of ruxolitinib and tofacitinib, the therapeutic use of JAK inhibitors (jakinibs) has expanded to include a large spectrum of diseases. Efficacy and safety data from over a decade of clinical studies have provided additional mechanistic insights while improving the care of patients with inflammatory and neoplastic conditions. This review discusses major advances in the field, focusing on updates in genetic diseases and in studies of clinical jakinibs in human disease.

Keywords

JAK; Jakinib; STAT; immunodeficiency; immunomodulation.

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