Single cell and spatial sequencing define processes by which keratinocytes and fibroblasts amplify inflammatory responses in psoriasis.

Autor: Ma F; Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.; Department of Dermatology, University of Michigan, Ann Arbor, MI, 48109, USA.; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA., Plazyo O; Department of Dermatology, University of Michigan, Ann Arbor, MI, 48109, USA., Billi AC; Department of Dermatology, University of Michigan, Ann Arbor, MI, 48109, USA., Tsoi LC; Department of Dermatology, University of Michigan, Ann Arbor, MI, 48109, USA., Xing X; Department of Dermatology, University of Michigan, Ann Arbor, MI, 48109, USA., Wasikowski R; Department of Dermatology, University of Michigan, Ann Arbor, MI, 48109, USA., Gharaee-Kermani M; Department of Dermatology, University of Michigan, Ann Arbor, MI, 48109, USA., Hile G; Department of Dermatology, University of Michigan, Ann Arbor, MI, 48109, USA., Jiang Y; Department of Dermatology, University of Michigan, Ann Arbor, MI, 48109, USA., Harms PW; Department of Dermatology, University of Michigan, Ann Arbor, MI, 48109, USA.; Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA., Xing E; Department of Dermatology, University of Michigan, Ann Arbor, MI, 48109, USA., Kirma J; Department of Dermatology, University of Michigan, Ann Arbor, MI, 48109, USA., Xi J; Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA., Hsu JE; Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA., Sarkar MK; Department of Dermatology, University of Michigan, Ann Arbor, MI, 48109, USA., Chung Y; Department of Dermatology, University of Michigan, Ann Arbor, MI, 48109, USA., Di Domizio J; Department of Dermatology, University Hospital of Lausanne, 1011, Lausanne, Switzerland., Gilliet M; Department of Dermatology, University Hospital of Lausanne, 1011, Lausanne, Switzerland., Ward NL; Department of Dermatology, Case Western Reserve University, Cleveland, OH, 44106, USA., Maverakis E; Department of Dermatology, University of California Davis, Sacramento, CA, USA., Klechevsky E; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA., Voorhees JJ; Department of Dermatology, University of Michigan, Ann Arbor, MI, 48109, USA., Elder JT; Department of Dermatology, University of Michigan, Ann Arbor, MI, 48109, USA.; Ann Arbor Veterans Affairs Medical Center, Ann Arbor, MI, 48105, USA., Lee JH; Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA., Kahlenberg JM; Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.; Department of Dermatology, University of Michigan, Ann Arbor, MI, 48109, USA., Pellegrini M; Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA, 90095, USA., Modlin RL; Division of Dermatology, Department of Medicine, University of California, Los Angeles, CA, 90095, USA.; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, 90095, USA., Gudjonsson JE; Department of Dermatology, University of Michigan, Ann Arbor, MI, 48109, USA. johanng@med.umich.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Jun 12; Vol. 14 (1), pp. 3455. Date of Electronic Publication: 2023 Jun 12.
DOI: 10.1038/s41467-023-39020-4
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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