IL-12 regulates type 3 immunity through interfollicular keratinocytes in psoriasiform inflammation
Pascale Zwicky, Florian Ingelfinger, Bruno Marcel Silva de Melo, Fiorella Ruchti, Stefanie Schärli, Nicole Puertas, Mirjam Lutz, Truong San Phan, Thomas M. Kündig, Mitchell P. Levesque, Julia‐Tatjana Maul, Christoph Schlapbach, Salomé LeibundGut‐Landmann, Sarah Mundt, Burkhard Becher
Abstract
germline knockout. Protective IL-12 signaling blocked the hyperproliferation of keratinocytes, maintained skin barrier integrity, and diminished disease-driving IL-23/type 3 immune circuits. In line, specific IL-23p19 blockade led to a more profound reduction of psoriatic keratinocyte expression signatures in the skin of patients with psoriasis than combined IL-12/IL-23 inhibition. Collectively, we provide a potential explanation for the superior efficacy of IL-23p19 inhibitors in psoriasis and describe an unperceived role of IL-12 in maintaining skin epithelial cell homeostasis.