The JAK/STAT Signaling Pathway: From Bench to Clinic

November 2021 in “ Signal Transduction and Targeted Therapy ”

Xiaofan Hu, Jing Li, Maorong Fu, Xia Zhao, Wei Wang

JAK/STAT signaling pathway Janus kinase signal transducer and activator of transcription JAK inhibitors alopecia areata hair loss

Studysummary This review discusses the composition, activation, and regulation of the JAK/STAT pathway and highlights its role and inhibitors in various diseases, but reports no new experimental results.

Our plain-language summary. Not medical advice or a treatment recommendation. Consult a qualified healthcare professional before changing treatment. Full disclaimer

The document discusses the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway, a crucial component in cellular processes like growth, differentiation, and immune response. Dysregulation of this pathway is linked to various cancers and autoimmune diseases. The pathway consists of ligand-receptor complexes, JAKs, and STATs, each with specific roles in biological processes. The document also explores the interaction between the JAK/STAT pathway and other pathways like TGFβ and MAPK. The JAK/STAT pathway is implicated in diseases like Hodgkin lymphoma, natural killer/T-cell lymphoma, myeloproliferative neoplasm, hepatocellular carcinoma, systemic lupus erythematosus, atopic dermatitis, rheumatoid arthritis, Parkinson's disease, hair loss, and age-related diseases. JAK inhibitors have shown potential in treating these conditions. The document also discusses the effectiveness of JAK inhibitors in treating diseases such as rheumatoid arthritis, inflammatory bowel disease, alopecia areata, COVID-19, and atopic dermatitis. The potential of natural compounds in regulating immune responses is also discussed. Future research should focus on understanding the JAK/STAT pathway's mechanisms, maximizing treatment efficacy while minimizing adverse effects, and exploring predictive and prognostic biomarkers.

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research Dermatological Effects of Curcuma Species: A Systematic Review

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This review synthesizes recent studies and suggests that Curcuma species may provide various dermatological benefits, but further research is needed to determine optimal delivery methods and dosages.

research A Subset of TREM2+ Dermal Macrophages Secretes Oncostatin M to Maintain Hair Follicle Stem Cell Quiescence and Inhibit Hair Growth

101 citations , March 2019 in “Cell Stem Cell”

This study found that Oncostatin M, via JAK-STAT5 signaling, keeps hair follicle stem cells inactive, and its removal leads to hair growth initiation in mice.

research JAK Inhibitors for Alopecia Areata: A Systematic Review and Meta-Analysis

130 citations , February 2019 in “JEADV. Journal of the European Academy of Dermatology and Venereology/Journal of the European Academy of Dermatology and Venereology”

This study found that JAK inhibitors for alopecia areata showed promising response rates, with 72.4% of 289 cases responding, and oral administration achieving better outcomes than topical treatment, but recurrence occurred when treatment stopped. Further large-scale studies are needed to confirm these findings.

research Tofacitinib for the Treatment of Severe Alopecia Areata and Variants: A Study of 90 Patients

238 citations , November 2016 in “Journal of The American Academy of Dermatology”

In this study, tofacitinib was reported to improve scalp hair regrowth in patients with severe alopecia areata, alopecia totalis, and alopecia universalis, showing a higher response in alopecia areata.

research STAT5 Activation in the Dermal Papilla Is Important for Hair Follicle Growth Phase Induction

32 citations , April 2016 in “Journal of Investigative Dermatology”

This study found that STAT5 activation in the dermal papilla acts as a key switch to trigger anagen entry in postdevelopmental hair follicle cycling.

research Pharmacologic Inhibition of JAK-STAT Signaling Promotes Hair Growth

159 citations , October 2015 in “Science Advances”

This study observed that applying JAK-STAT pathway inhibitors to mouse and human skin led to rapid hair growth by inducing the anagen phase of hair follicles.

research Calcineurin/NFATc1 Signaling Links Skin Stem Cell Quiescence to Hormonal Signaling During Pregnancy and Lactation

40 citations , April 2014 in “Genes & Development”

The researchers reported that in mice, prolactin signaling in the skin epithelium inhibits hair follicle stem cell activation, promoting quiescence during periods of high serum prolactin like pregnancy and lactation.

research Age-Associated Inflammation Inhibits Epidermal Stem Cell Function

144 citations , September 2012 in “Genes & development”

This study found that aging in the epidermis disrupts cytokine balance and stem cell function, which may contribute to broader tumor-suppressive mechanisms.

research SKPs Derive from Hair Follicle Precursors and Exhibit Properties of Adult Dermal Stem Cells

330 citations , December 2009 in “Cell stem cell”

This study suggests that skin-derived precursors from Sox2(+) hair follicle dermal cells have the potential to function as dermal stem cells, supporting hair morphogenesis, dermal maintenance, and wound-healing.

research Scratching the Surface of Skin Development

788 citations , February 2007 in “Nature”

This review explores how adult skin epithelia preserve stem cell populations for hair follicle regeneration and wound healing, but reports no new experimental results.

research Interleukin 6: Insights Into Its Function in Skin by Overexpression in Transgenic Mice

221 citations , June 1992 in “Proceedings of the National Academy of Sciences”

In this study, IL-6 expression in transgenic mice thickened the stratum corneum without causing increased epidermal proliferation or inflammation, suggesting it may enhance skin protection rather than directly induce inflammation.