Differentiation of IL-26+ TH17 intermediates into IL-17A producers via epithelial crosstalk in psoriasis

Autor: Anissa Fries, Fanny Saidoune, François Kuonen, Isabelle Dupanloup, Nadine Fournier, Ana Cristina Guerra de Souza, Muzlifah Haniffa, Feiyang Ma, Johann E. Gudjonsson, Lennart Roesner, Yang Li, Thomas Werfel, Curdin Conrad, Raphael Gottardo, Robert L. Modlin, Jeremy Di Domizio, Michel Gilliet
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Nature Communications, Vol 14, Iss 1, Pp 1-14 (2023)
Druh dokumentu: article
ISSN: 2041-1723
49605240
DOI: 10.1038/s41467-023-39484-4
Popis: Abstract Interleukin (IL)-26 is a TH17 cytokine with known antimicrobial and pro-inflammatory functions. However, the precise role of IL-26 in the context of pathogenic TH17 responses is unknown. Here we identify a population of blood TH17 intermediates that produce high levels of IL-26 and differentiate into IL-17A-producing TH17 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+ TH17 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 TH17 cells that infiltrates psoriatic skin and controls its own maturation into IL17A-producing TH17 cells, via epithelial crosstalk involving paracrine production of TGF-β1.
Databáze: Directory of Open Access Journals
Externí odkaz: