Single cell and spatial sequencing define processes by which keratinocytes and fibroblasts amplify inflammatory responses in psoriasis
Year: 2023
Type: article
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.
Source: Nature Communications
Authors: 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
Institutions: University of Michigan, Michigan Medicine, Centre Hospitalier Universitaire Vaudois, Case Western Reserve University, University of California Davis Medical Center, University of California, Davis, Washington University in St. Louis, Ann Arbor VA Medical Center, University of California, Los Angeles
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,290
Funders: National Science Foundation, Dermatology Foundation, National Psoriasis Foundation, A. Alfred Taubman Medical Research Institute, National Research Foundation, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: G1072856781, G1093691342, G1498502315, Integrative Biology Approach to Identify and Characterize Roles of lncRNAs Associated with Psoriasis Pathology, G1844704720, G2178644687, G3124041251, G3223806668, G3251550854, G3335544242, Linkage Analysis of Familial Psoriasis, G4166503464, G537629116, CD1-restricted T-cell Responses in Skin, ELLIPSS: ELucidating the Landscape of Immunoendotypes in Psoriatic Skin and Synovium, Identity and function of IL-26-producing T cells
OpenAlex ID: W4380368096