Differentiation of IL-26+ TH17 intermediates into IL-17A producers via epithelial crosstalk in psoriasis
Anissa Fries, Fanny Saidoune, François Kuonen, Isabelle Dupanloup, Nadine Fournier, Ana Cristina Guerra Souza, Muzlifah Haniffa, Feiyang Ma, Jóhann E. Guðjónsson, Lennart M. Roesner, Yang Li, Thomas Werfel, Curdin Conrad, Raphaël Gottardo, Robert L. Modlin, Jérémy Di Domizio, Michel Gilliet
Abstract
Abstract Interleukin (IL)-26 is a T H 17 cytokine with known antimicrobial and pro-inflammatory functions. However, the precise role of IL-26 in the context of pathogenic T H 17 responses is unknown. Here we identify a population of blood T H 17 intermediates that produce high levels of IL-26 and differentiate into IL-17A-producing T H 17 cells upon TGF-β1 exposure. By combining single cell RNA sequencing, TCR sequencing and spatial transcriptomics we show that this process occurs in psoriatic skin. In fact, IL-26+ T H 17 intermediates infiltrating psoriatic skin induce TGF-β1 expression in basal keratinocytes and thereby promote their own differentiation into IL-17A-producing cells. Thus, our study identifies IL-26-producing cells as an early differentiation stage of T H 17 cells that infiltrates psoriatic skin and controls its own maturation into IL17A-producing T H 17 cells, via epithelial crosstalk involving paracrine production of TGF-β1.