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Cited by 1,206Cytokine Signaling Pathways and InteractionsRheumatoid Arthritis Research and TherapiesAutoimmune and Inflammatory Disorders Research

JAK–STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects

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Banerjee, Shubhasree, Biehl, Ann, Gadina, Massimo, Hasni, Sarfaraz, Schwartz, Daniella M.·2017·Drugs
DOI 10.1007/s40265-017-0701-9PMC PMC7102286
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Abstract

The Janus kinase/signal transduction and activator of transcription (JAK-STAT) signaling pathway is implicated in the pathogenesis of inflammatory and autoimmune diseases including rheumatoid arthritis, psoriasis, and inflammatory bowel disease. Many cytokines involved in the pathogenesis of autoimmune and inflammatory diseases use JAKs and STATs to transduce intracellular signals. Mutations in JAK and STAT genes cause a number of immunodeficiency syndromes, and polymorphisms in these genes are associated with autoimmune diseases. The success of small-molecule JAK inhibitors (Jakinibs) in the treatment of rheumatologic disease demonstrates that intracellular signaling pathways can be targeted therapeutically to treat autoimmunity. Tofacitinib, the first rheumatologic Jakinib, is US Food and Drug Administration (FDA) approved for rheumatoid arthritis and is currently under investigation for other autoimmune diseases. Many other Jakinibs are in preclinical development or in various phases of clinical trials. This review describes the JAK-STAT pathway, outlines its role in autoimmunity, and explains the rationale/pre-clinical evidence for targeting JAK-STAT signaling. The safety and clinical efficacy of the Jakinibs are reviewed, starting with the FDA-approved Jakinib tofacitinib, and continuing on to next-generation Jakinibs. Recent and ongoing studies are emphasized, with a focus on emerging indications for JAK inhibition and novel mechanisms of JAK-STAT signaling blockade.

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  • Early microglial changes included significant upregulation of gene sets involved in inflammatory processes, interferon response, Fc receptors, MHC class II components, and complement components.

    “Early changes included significant upregulation of gene sets involved in inflammatory processes (IL1B, CSF1R, STAB1, NINJ1, JAK3)61–65, interferon response (IRF1, IRF7, IFI16), Fc receptors (FCGR1A, FCGR1B, FCGR2A, FCGR3B), components of the class II major histocompatibility complex (MHC) (CD74, HLA-DRB5) and complement components (C1QA, C1QB) (Fig. 6d, top, red).”

    From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [62]

    In “Implications of the JAK–STAT Pathway in Inflammatory and Autoimmune Diseases” (page unavailable), the review links JAK3 to immune-cell function and discusses JAK3 blockade as a potential immunosuppressive therapy. That supports the inflammatory relevance of JAK3, the gene within the citation’s scope, but the paper does not report early microglial changes or significant upregulation of the listed gene set. (LLM, conf=0.78)

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Cited by

Sorted by citations

Authors
Banerjee, S., Biehl, A., Gadina, M., Hasni, S., & Schwartz, D. M.
Affiliations
National Institutes of Health (US)
Corresponding author
Banerjee, Shubhasree
ORCID
Venue
Drugs
Publisher
Springer Science and Business Media LLC
Published
2017-03-03
Volume
77
Issue
5
Pages
521-546
ISSN
  • 0012-6667 (ISSN-L)
  • 1179-1950
DOI
10.1007/s40265-017-0701-9
PMC
PMC7102286
OpenAlex
W4211144854
Cited by
1,206
References
2
Citations by year
2026: 111 · 2025: 173 · 2024: 226 · 2023: 189 · 2022: 163 · 2021: 123 · 2020: 85 · 2019: 69 · 2018: 47 · 2017: 17
FWCI
6.25
Type
journal article
Language
en
Update notices
Open access
Licence
Locations
  • Drugs (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
  • Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
Keywords
JAK/STAT signaling, JAK inhibitors, tofacitinib, rheumatoid arthritis, psoriasis, inflammatory bowel disease, autoimmune disease, cytokine signaling, immunodeficiency
MeSH terms
Autoimmune Diseases, Humans, Inflammation, Signal Transduction, Protein Kinase Inhibitors, STAT Transcription Factors, Janus Kinases

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