학술논문
Single cell and spatial sequencing define processes by which keratinocytes and fibroblasts amplify inflammatory responses in psoriasis
Document Type
article
Author
Feiyang Ma; Olesya Plazyo; Allison C. Billi; Lam C. Tsoi; Xianying Xing; Rachael Wasikowski; Mehrnaz Gharaee-Kermani; Grace Hile; Yanyun Jiang; Paul W. Harms; Enze Xing; Joseph Kirma; Jingyue Xi; Jer-En Hsu; Mrinal K. Sarkar; Yutein Chung; Jeremy Di Domizio; Michel Gilliet; Nicole L. Ward; Emanual Maverakis; Eynav Klechevsky; John J. Voorhees; James T. Elder; Jun Hee Lee; J. Michelle Kahlenberg; Matteo Pellegrini; Robert L. Modlin; Johann E. Gudjonsson
Source
Nature Communications, Vol 14, Iss 1, Pp 1-19 (2023)
Subject
Language
English
ISSN
2041-1723
Abstract
Abstract The immunopathogenesis of psoriasis, a common chronic inflammatory disease of the skin, is incompletely understood. Here we demonstrate, using a combination of single cell and spatial RNA sequencing, IL-36 dependent amplification of IL-17A and TNF inflammatory responses in the absence of neutrophil proteases, which primarily occur within the supraspinous layer of the psoriatic epidermis. We further show that a subset of SFRP2 + fibroblasts in psoriasis contribute to amplification of the immune network through transition to a pro-inflammatory state. The SFRP2 + fibroblast communication network involves production of CCL13, CCL19 and CXCL12, connected by ligand-receptor interactions to other spatially proximate cell types: CCR2 + myeloid cells, CCR7 + LAMP3 + dendritic cells, and CXCR4 expressed on both CD8+ Tc17 cells and keratinocytes, respectively. The SFRP2 + fibroblasts also express cathepsin S, further amplifying inflammatory responses by activating IL-36G in keratinocytes. These data provide an in-depth view of psoriasis pathogenesis, which expands our understanding of the critical cellular participants to include inflammatory fibroblasts and their cellular interactions.