JAK inhibitors in dermatology: The promise of a new drug class
William Damsky,Brett A. King +1 more
TLDR
Evidence suggests that JAK inhibition might be broadly useful in dermatology, with early reports of efficacy in several other conditions, and JAK inhibitors can be administered orally or used topically and represent a promising new class of medications.Abstract:
New molecularly targeted therapeutics are changing dermatologic therapy. Janus kinase–signal transducer and activator of transcription (JAK-STAT) is an intracellular signaling pathway upon which many different proinflammatory signaling pathways converge. Numerous inflammatory dermatoses are driven by soluble inflammatory mediators, which rely on JAK-STAT signaling, and inhibition of this pathway using JAK inhibitors might be a useful therapeutic strategy for these diseases. Growing evidence suggests that JAK inhibitors are efficacious in atopic dermatitis, alopecia areata, psoriasis, and vitiligo. Additional evidence suggests that JAK inhibition might be broadly useful in dermatology, with early reports of efficacy in several other conditions. JAK inhibitors can be administered orally or used topically and represent a promising new class of medications. The use of JAK inhibitors in dermatology is reviewed here.read more
Citations
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Synergism of TNF-α and IFN-γ Triggers Inflammatory Cell Death, Tissue Damage, and Mortality in SARS-CoV-2 Infection and Cytokine Shock Syndromes
Rajendra Karki,Bhesh Raj Sharma,Shraddha Tuladhar,Evan P. Williams,Lillian Zalduondo,Parimal Samir,Min Zheng,Balamurugan Sundaram,Balaji Banoth,R. K. Subbarao Malireddi,Patrick Schreiner,Geoffrey Neale,Peter Vogel,Richard Webby,Colleen B. Jonsson,Thirumala-Devi Kanneganti +15 more
TL;DR: It is suggested that blocking the cytokine-mediated inflammatory cell death signaling pathway identified here may benefit patients with COVID-19 or other infectious and autoinflammatory diseases by limiting tissue damage/inflammation.
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Update on the Pathomechanism, Diagnosis, and Treatment Options for Rheumatoid Arthritis.
TL;DR: This review summarizes the current understanding of the underlying pathomechanism, diagnosis of RA, as well as the mode of action, clinical benefits, and side-effects of the currently available DMARDs.
Journal ArticleDOI
Novel therapies for immune-mediated inflammatory diseases: What can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn’s disease and ulcerative colitis?
TL;DR: This review summarises the development and recent application of Janus kinase (JAK) inhibitors in the treatment of IMIDs, including first-generation pan-JAK inhibitors (tofacitinib, baricit inib, ruxolitinIB, peficitinib) and second-generation selective JAK inhibitor(s) (decernotinib, filgotin ib, upadacit inib).
Journal ArticleDOI
Targeting JAK-STAT Signaling to Control Cytokine Release Syndrome in COVID-19.
TL;DR: The possibilities and challenges of targeting the pathway in COVID-19 are reviewed, and JAK inhibition presents an attractive therapeutic strategy for CRS, which is a common cause of adverse clinical outcomes in CO VID-19.
Journal ArticleDOI
Jak Stat signaling and cancer: Opportunities, benefits and side effects of targeted inhibition.
TL;DR: The direct and mediated mechanisms of Jak stat signaling in and on tumors cells, the interactions with other signaling pathways and transcription factors and the targeting of the functionally crucial secondary modifications of Stat molecules suggest novel approaches to the future development of Jak Stat based cancer therapeutics.
References
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Journal ArticleDOI
STAT3 Mutations in the Hyper-IgE Syndrome
Steven M. Holland,Frank R. DeLeo,Houda Elloumi,Amy P. Hsu,Gulbu Uzel,Nina N. Brodsky,Alexandra F. Freeman,Andrew P. Demidowich,Joie Davis,Maria L. Turner,Victoria L. Anderson,Dirk Darnell,Pamela Welch,Douglas B. Kuhns,David M. Frucht,Harry L. Malech,John I. Gallin,Scott D. Kobayashi,Adeline R. Whitney,Jovanka M. Voyich,James M. Musser,Cristina Woellner,Alejandro A. Schäffer,Jennifer M. Puck,Bodo Grimbacher +24 more
TL;DR: Mutations in STAT3 underlie sporadic and dominant forms of the hyper-IgE syndrome, an immunodeficiency syndrome involving increased innate immune response, recurrent infections, and complex somatic features.
Journal ArticleDOI
The JAK-STAT Pathway: Impact on Human Disease and Therapeutic Intervention*
John J. O'Shea,Daniella M. Schwartz,Alejandro V. Villarino,Massimo Gadina,Iain B. McInnes,Arian Laurence +5 more
TL;DR: The Janus kinase (JAK)-signal transducer of activators of transcription (STAT) pathway is now recognized as an evolutionarily conserved signaling pathway employed by diverse cytokines, interferons, growth factors, and related molecules.
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Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID).
Paolo Macchi,Anna Villa,Silvia Giliani,Maria Grazia Sacco,Annalisa Frattini,Fulvio Porta,A. G. Ugazio,J A Johnston,Fabio Candotti,John J. O'Shea +9 more
TL;DR: Two unrelated T- B+SCID patients who have homozygous mutations in the gene for Jak-3 are investigated and abnormalities in the Jak/STAT signalling pathway can account for SCID in humans.
Journal ArticleDOI
Mutation of Jak3 in a Patient with SCID: Essential Role of Jak3 in Lymphoid Development
Sarah M. Russell,Nahid Tayebi,Hiroshi Nakajima,M. C. Riedy,Joseph L. Roberts,M. Javad Aman,Thi-Sau Migone,Masayuki Noguchi,M. Louise Markert,Rebecca H. Buckley,John J. O'Shea,Warren J. Leonard +11 more
TL;DR: Observations indicate that the functions of γc are dependent on Jak3 and that Jak3 is essential for lymphoid development and signaling.
Journal ArticleDOI
Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition
Luzhou Xing,Z. Dai,Ali Jabbari,Jane E. Cerise,Claire A. Higgins,Weijuan Gong,Annemieke de Jong,Sivan Harel,Gina M. DeStefano,Lisa Rothman,Pallavi Singh,Lynn Petukhova,Julian Mackay-Wiggan,Angela M. Christiano,Raphael Clynes +14 more
TL;DR: It is shown that cytotoxic CD8+NKG2D+ T cells are both necessary and sufficient for the induction of AA in mouse models of disease, suggesting the potential clinical utility of JAK inhibition in human AA.