Figure - PMC

Skip to main content

View full-text article in PMC

. Author manuscript; available in PMC: 2023 May 8.

Published in final edited form as: J Allergy Clin Immunol. 2021 Aug 24;148(4):927–940. doi: 10.1016/j.jaci.2021.08.009

Figure 1. — (A) Cytokine binding induces receptor subunit dimerization which leads to intracellular phosphorylation by janus kinase (JAK) proteins. Signal transducer and activator of transcription (STAT) proteins are then recruited to the phosphorylated receptor and phosphorylated by JAK proteins. Phosphorylated STAT proteins dimerize and translocate to the nucleus to regulate gene transcription. (B) Cytokines bind to JAK-STAT dependent receptors to propagate inflammation and itch in atopic dermatitis (AD). IL-4 binds to a heterodimer consisting of the IL-4Rα and common gamma chain (γc) subunits and is dependent on JAK1/3. IL-13 binds to a heterodimer consisting of IL-4Rα and IL-13Rα1 (JAK1/2, TYK2), while IL-31, IL-22, and TSLP bind to IL-31Rα / OSM, IL-22Rα1 / IL-10Rβ2, and CRLF2 / IL-7Rα heterodimers, respectively (JAK1/2). IL-5, which has less clear functional significance in AD, binds to the IL-5Rα and cytokine receptor common subunit beta (βc) heterodimer (JAK1/2). Topical and oral JAK inhibitors reversibly inhibit JAK proteins with varying specificity: abrocitinib and upadacitinib (JAK1); ruxolitinib and baricitinib (JAK1/2); tofacitinib (JAK1/3); and delgocitinib (JAK1/2/3,TYK2). Biologic monoclonal antibody therapies inhibit upstream cytokine signaling. Dupilumab binds to the IL-4Rα receptor subunit shared by IL-4 and IL-13. Emerging biologic therapies for AD include lebrikizumab and tralokinumab (IL-13) and nemolizumab (IL-31Rα).

Figure 1. — (A) Cytokine binding induces receptor subunit dimerization which leads to intracellular phosphorylation by janus kinase (JAK) proteins. Signal transducer and activator of transcription (STAT) proteins are then recruited to the phosphorylated receptor and phosphorylated by JAK proteins. Phosphorylated STAT proteins dimerize and translocate to the nucleus to regulate gene transcription. (B) Cytokines bind to JAK-STAT dependent receptors to propagate inflammation and itch in atopic dermatitis (AD). IL-4 binds to a heterodimer consisting of the IL-4Rα and common gamma chain (γc) subunits and is dependent on JAK1/3. IL-13 binds to a heterodimer consisting of IL-4Rα and IL-13Rα1 (JAK1/2, TYK2), while IL-31, IL-22, and TSLP bind to IL-31Rα / OSM, IL-22Rα1 / IL-10Rβ2, and CRLF2 / IL-7Rα heterodimers, respectively (JAK1/2). IL-5, which has less clear functional significance in AD, binds to the IL-5Rα and cytokine receptor common subunit beta (βc) heterodimer (JAK1/2). Topical and oral JAK inhibitors reversibly inhibit JAK proteins with varying specificity: abrocitinib and upadacitinib (JAK1); ruxolitinib and baricitinib (JAK1/2); tofacitinib (JAK1/3); and delgocitinib (JAK1/2/3,TYK2). Biologic monoclonal antibody therapies inhibit upstream cytokine signaling. Dupilumab binds to the IL-4Rα receptor subunit shared by IL-4 and IL-13. Emerging biologic therapies for AD include lebrikizumab and tralokinumab (IL-13) and nemolizumab (IL-31Rα).