Journal article
An overview of JAK/STAT pathways and JAK inhibition in alopecia areata
Frontiers in immunology, Vol.13, 955035
08/01/2022
DOI: 10.3389/fimmu.2022.955035
PMCID: PMC9470217
PMID: 36110853
Abstract
Alopecia Areata (AA) is a common autoimmune disease characterized by non-scarring hair loss ranging from patches on the scalp to complete hair loss involving the entire body. Disease onset is hypothesized to follow the collapse of immune privilege of the hair follicle, which results in an increase in self-peptide/MHC expression along the follicular epithelium. Hair loss is associated with infiltration of the hair follicle with putatively self-reactive T cells. This process is thought to skew the hair follicle microenvironment away from a typically homeostatic immune state towards one of active inflammation. This imbalance is mediated in part by the dominating presence of specific cytokines. While interferon-γ (IFNγ) has been identified as the key player in AA pathogenesis, many other cytokines have also been shown to play pivotal roles. Mechanistic studies in animal models have highlighted the contribution of common gamma chain (γc) cytokines such as IL-2, IL-7, and IL-15 in augmenting disease. IFNγ and γc cytokines signal through pathways involving receptor activation of Janus kinases (JAKs) and signal transducers and activators of transcription (STATs). Based on these findings, JAK/STAT pathways have been targeted for the purposes of therapeutic intervention in the clinical setting. Case reports and series have described use of small molecule JAK inhibitors leading to hair regrowth among AA patients. Furthermore, emerging clinical trial results show great promise and position JAK inhibitors as a treatment strategy for patients with severe or recalcitrant disease. Demonstrated efficacy from large-scale clinical trials of the JAK inhibitor baricitinib led to the first-in-disease FDA-approved treatment for AA in June of 2022. This review aims to highlight the JAK/STAT signaling pathways of various cytokines involved in AA and how targeting those pathways may impact disease outcomes in both laboratory and clinical settings.
Details
- Title: Subtitle
- An overview of JAK/STAT pathways and JAK inhibition in alopecia areata
- Creators
- Maddison Lensing - University of IowaAli Jabbari - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Frontiers in immunology, Vol.13, 955035
- DOI
- 10.3389/fimmu.2022.955035
- PMID
- 36110853
- PMCID
- PMC9470217
- NLM abbreviation
- Front Immunol
- ISSN
- 1664-3224
- eISSN
- 1664-3224
- Publisher
- Frontiers Media S.A
- Grant note
- DOI: 10.13039/100000738, name: U.S. Department of Veterans Affairs, award: I01 BX004907; DOI: 10.13039/100000002, name: National Institutes of Health, award: R01 AR077194 , K08 AR069111
- Language
- English
- Date published
- 08/01/2022
- Academic Unit
- Dermatology; Neuroscience and Pharmacology
- Record Identifier
- 9984296286402771
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