Role of the JAK/STAT signaling pathway in regulation of innate immunity in neuroinflammatory diseases
Open accessAbstract
The Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) signaling pathway is utilized by numerous cytokines and interferons, and is essential for the development and function of both innate and adaptive immunity. Aberrant activation of the JAK/STAT pathway is evident in neuroinflammatory diseases such as Multiple Sclerosis and Parkinson's Disease. Innate immunity is the front line defender of the immune system and is composed of various cell types, including microglia, macrophages and neutrophils. Innate immune responses have both pathogenic and protective roles in neuroinflammation, depending on disease context and the microenvironment in the central nervous system. In this review, we discuss the role of innate immunity in the pathogenesis of neuroinflammatory diseases, how the JAK/STAT signaling pathway regulates the innate immune response, and finally, the potential for ameliorating neuroinflammation by utilization of JAK/STAT inhibitors.
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When macrophages encounter foreign molecules, they are activated by up-regulation of NF-kβ, which, together with JAK-STAT-induced inflammatory cytokines, increases iNOS expression and •NO production.
“When macrophages encounter foreign molecules, they are activated by up-regulation of NF-kβ, which, together with JAK-STAT-induced inflammatory cytokines, increases iNOS expression and •NO production [118].”
From The Role of Reactive Species on Innate Immunity (2022) · cites this paper as [118]
Cytokines bind to receptors in the microglia and activate the JAK/STAT signaling pathway.
“Cytokines bind to receptors in the microglia and activate the JAK/STAT signaling pathway (Yan et al., 2016).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Yan et al., 2016
This pathway plays a critical role in the initiation and regulation of innate immune responses and adaptive immunity.
“This pathway plays a critical role in the initiation and regulation of innate immune responses and adaptive immunity (Yan et al., 2016).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Yan et al., 2016
PI3k-Akt and JAK-STAT signalling are central regulators of microglial mediated neuroinflammation.
“This included PI3k-Akt and JAK-STAT signalling, central regulators of microglial mediated neuroinflammation63,64.”
From Mouse microglia express unique miRNA-mRNA networks to facilitate age-specific functions in the developing central nervous system (2023) · cites this paper as [63]
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- Authors
- Yan, Z., Gibson, S. A., Buckley, J. A., Qin, H., & Benveniste, E. N.
- Affiliations
- University of Alabama at Birmingham (US)
- Corresponding author
- Qin, Hongwei
- Benveniste, Etty N.
- Venue
- Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2018-04
- Volume
- 189
- Pages
- 4-13
- ISSN
- 1521-6616 (ISSN-L)
- PMC
- PMC5573639
- OpenAlex
- W2528968729
- Cited by
- 318
- References
- 154
- Citations by year
- 2026: 30 · 2025: 46 · 2024: 65 · 2023: 44 · 2022: 40 · 2021: 33 · 2020: 27 · 2019: 17 · 2018: 10 · 2017: 5
- FWCI
- 5.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health Grants (NS45290, NS57563)
- UAB Multiple Sclerosis Center (T32 AI007051)
- Michael J. Fox Foundation (7550.02)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- JAK/STAT signaling, innate immunity, neuroinflammation, multiple sclerosis, Parkinson's disease, microglia, macrophages, neutrophils, cytokines, interferon, JAK/STAT inhibitors
- MeSH terms
- Humans, Immunity, Innate, Macrophages, Multiple Sclerosis, Parkinson Disease, Signal Transduction, Microglia, Models, Immunological, STAT Transcription Factors, Janus Kinases
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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