银屑病中上皮细胞串扰将 IL-26 T17 中间产物分化为 IL-17A 产生细胞。
Differentiation of IL-26 T17 intermediates into IL-17A producers via epithelial crosstalk in psoriasis.
机构信息
Department of Dermatology, CHUV University Hospital and University of Lausanne (UNIL), Lausanne, Switzerland.
Translational Data Science Facility, Agora Cancer Research Center, Swiss Institute of Bioinformatics, Lausanne, Switzerland.
出版信息
Nat Commun. 2023 Jun 30;14(1):3878. doi: 10.1038/s41467-023-39484-4.
Interleukin (IL)-26 is a T17 cytokine with known antimicrobial and pro-inflammatory functions. However, the precise role of IL-26 in the context of pathogenic T17 responses is unknown. Here we identify a population of blood T17 intermediates that produce high levels of IL-26 and differentiate into IL-17A-producing T17 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+ T17 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 T17 cells that infiltrates psoriatic skin and controls its own maturation into IL17A-producing T17 cells, via epithelial crosstalk involving paracrine production of TGF-β1.
白细胞介素 (IL)-26 是一种 T17 细胞因子，具有已知的抗菌和促炎功能。然而，IL-26 在致病性 T17 反应中的精确作用尚不清楚。在这里，我们鉴定了一群血液 T17 中间产物，它们产生高水平的 IL-26，并在 TGF-β1 暴露下分化为产生 IL-17A 的 T17 细胞。通过结合单细胞 RNA 测序、TCR 测序和空间转录组学，我们表明这一过程发生在银屑病皮肤中。事实上，浸润银屑病皮肤的 IL-26+T17 中间产物诱导基底角质形成细胞中 TGF-β1 的表达，从而促进其自身分化为产生 IL-17A 的细胞。因此，我们的研究将产生 IL-26 的细胞鉴定为浸润银屑病皮肤的 T17 细胞的早期分化阶段，并通过涉及 TGF-β1 旁分泌产生的上皮细胞串扰来控制其自身成熟为产生 IL17A 的 T17 细胞。
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