Single cell and spatial sequencing define processes by which keratinocytes and fibroblasts amplify inflammatory responses in psoriasis.
In: Nature communications, vol 14, iss 1, 2023
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Zugriff:
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.
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Single cell and spatial sequencing define processes by which keratinocytes and fibroblasts amplify inflammatory responses in psoriasis.
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Autor/in / Beteiligte Person: | Ma, Feiyang ; Plazyo, Olesya ; Billi, Allison C ; Tsoi, Lam C ; Xing, Xianying ; Wasikowski, Rachael ; Gharaee-Kermani, Mehrnaz ; Hile, Grace ; Jiang, Yanyun ; Harms, Paul W ; Xing, Enze ; Kirma, Joseph ; Xi, Jingyue ; Hsu, Jer-En ; Sarkar, Mrinal K ; Chung, Yutein ; Di Domizio, Jeremy ; Gilliet, Michel ; Ward, Nicole L ; Maverakis, Emanual ; Klechevsky, Eynav ; Voorhees, John J ; Elder, James T ; Lee, Jun Hee ; Kahlenberg, J Michelle ; Pellegrini, Matteo ; Modlin, Robert L ; Gudjonsson, Johann E |
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Zeitschrift: | Nature communications, vol 14, iss 1, 2023 |
Veröffentlichung: | eScholarship, University of California, 2023 |
Medientyp: | academicJournal |
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