Differentiation of IL-26<sup>+</sup> T<sub>H</sub>17 intermediates into IL-17A producers via epithelial crosstalk in psoriasis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37391412.
- Also identified by DOI 10.1038/s41467-023-39484-4 and PMC identifier 10313793.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Interleukin (IL)-26 is a T<sub>H</sub>17 cytokine with known antimicrobial and pro-inflammatory functions. However, the precise role of IL-26 in the context of pathogenic T<sub>H</sub>17 responses is unknown. Here we identify a population of blood T<sub>H</sub>17 intermediates that produce high levels of IL-26 and differentiate into IL-17A-producing T<sub>H</sub>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<sub>H</sub>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<sub>H</sub>17 cells that infiltrates psoriatic skin and controls its own maturation into IL17A-producing T<sub>H</sub>17 cells, via epithelial crosstalk involving paracrine production of TGF-β1.
Medical subject headings
- Transforming Growth Factor beta1
- Psoriasis