Dissecting key contributions of TH2 and TH17 cytokines to atopic dermatitis pathophysiology
Luca D. Meesters, Janou A. Y. Roubroeks, Aranka Gerritsen, Niels Velthuijs, Jaimy A Klijnhout, Camille Laberthonnìère, I.M. van Vlijmen-Willems, Matthias Hübenthal, Diana Rodijk‐Olthuis, Rens H.W. Peters, Gijs Rikken, Silke Szymczak, Nanna Fyhrquist, Harri Alenius, Stephan Weidinger, Jos P.H. Smits, Musa M. Mhlanga, Huiqing Zhou, Hanna Niehues, Ellen H. van den Bogaard
Abstract
BACKGROUND: In atopic dermatitis (AD), epidermal disease hallmarks are driven by a complex cutaneous inflammatory milieu that varies between patients. How these variable inflammatory signals affect cellular and molecular epidermal AD phenotypes is difficult to study in vivo. OBJECTIVE: We aimed to unravel which AD-associated cytokines drive specific epidermal disease hallmarks. METHODS: 22 cytokines. RESULTS: 2 + IL-22 such as downregulated ACER1 and AKR1C3. Gene expression levels were restored by combinatory exposure to the aryl hydrocarbon receptor ligand tapinarof and the Janus kinase inhibitor tofacitinib. This combined therapeutic approach also completely restored epidermal barrier function and improved morphologic disease hallmarks. CONCLUSION: 2-driven acute AD pathophysiology and highlight the potential of combinatory medicine in targeted treatment of AD.