No abstract

No abstract

Dozens of cytokines that bind Type I and Type II receptors use the Janus Kinases (JAK) and the Signal Transducer and Activator of Transcription (STAT) proteins pathway for intracellular signaling, orchestrating hematopoiesis, inducing inflammation, and controlling the immune response. Currently, oral JAK inhibitors are being used to treat many inflammatory and myeloproliferative diseases and are also under investigation in several clinical trials for skin diseases. Thus, dermatologists should understand how the JAK-STAT pathway works as well as the mechanism of action of the JAK inhibitors which will certainly become an important part of the dermatologist’s treatment armamentarium in the next few years. Keywords: JAK inhibitors; Janus Kinases; JAK-STAT Pathway List of Abbreviations: AD: Atopic Dermatitis ADP: Adenosine diphosphate Dmards: Disease-Modifying Antirheumatic Drugs JAK: Janus kinase(s) Jaki: Janus kinase Inhibitor(s) PIAS: Protein Inhibitor of Activated STAT P-STAT: Phosphorylated STAT STAT: Signal Transducer and Activator of Transcription TYK2: Tyrosine Kinase 2 Wsxws: Tryptophan-Serine-X-Tryptophan-Serine

Interleukins (IL) IL-4 and IL-13 are key players in diseases in which the Type 2 immune response is predominant, such as atopic dermatitis (AD), asthma, and chronic rhinosinusitis with nasal polyposis (CRSwNP), that are currently being treated with dupilumab. Dupilumab is a fully human IgG4 monoclonal antibody that targets the IL-4 receptor alpha chain (IL-4Rα), preventing both IL-4 and IL-13 mediated signaling. This mini-review summarizes the IL-4 receptor system as well as the mechanism of action of dupilumab. Keywords: IL-4; IL-13; dupilumab; Type 2 immunity Abbreviations AD: Atopic Dermatitis CRSwNP: Chronic Rhinosinusitis with Nasal Polyps DNA: Deoxyribonucleic Acid JAK: Janus Kinase IL: Interleukin IL-4R: Interleukin 4 Receptor IL-4Rα: Interleukin 4 Receptor alpha chain IL-13Rα1: Interleukin 13 Receptor alpha 1 chain IL-13Rα2:Interleukin 13 Receptor alpha 2 chain STAT: Signal Transducer and Activator of Transcription TGF-β: Transforming Growth Factor beta TNF: Tumor Necrosis Factor TYK2: Tyrosine Kinase 2 γc: Common gamma chain