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Schäbitz, A.* ; Hillig, C. ; Mubarak, M. ; Jargosch, M. ; Farnoud, A. ; Scala, E.* ; Kurzen, N. ; Pilz, A.C.* ; Bhalla, N.* ; Thomas, J. ; Stahle, M.* ; Biedermann, T.* ; Schmidt-Weber, C.B. ; Theis, F.J. ; Garzorz-Stark, N.* ; Eyerich, K.* ; Menden, M.P. ; Eyerich, S.

Spatial transcriptomics landscape of lesions from non-communicable inflammatory skin diseases.

Nat. Commun. 13:7729 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Abundant heterogeneous immune cells infiltrate lesions in chronic inflammatory diseases and characterization of these cells is needed to distinguish disease-promoting from bystander immune cells. Here, we investigate the landscape of non-communicable inflammatory skin diseases (ncISD) by spatial transcriptomics resulting in a large repository of 62,000 spatially defined human cutaneous transcriptomes from 31 patients. Despite the expected immune cell infiltration, we observe rather low numbers of pathogenic disease promoting cytokine transcripts (IFNG, IL13 and IL17A), i.e. >125 times less compared to the mean expression of all other genes over lesional skin sections. Nevertheless, cytokine expression is limited to lesional skin and presented in a disease-specific pattern. Leveraging a density-based spatial clustering method, we identify specific responder gene signatures in direct proximity of cytokines, and confirm that detected cytokine transcripts initiate amplification cascades of up to thousands of specific responder transcripts forming localized epidermal clusters. Thus, within the abundant and heterogeneous infiltrates of ncISD, only a low number of cytokine transcripts and their translated proteins promote disease by initiating an inflammatory amplification cascade in their local microenvironment.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Atopic-dermatitis; Gene-expression; T-cells; Autoimmunity; Psoriasis
Sprache englisch
Veröffentlichungsjahr 2022
HGF-Berichtsjahr 2022
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 13, Heft: 1, Seiten: , Artikelnummer: 7729 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Allergy Research (IAF)
Institute of Computational Biology (ICB)
POF Topic(s) 30202 - Environmental Health
30205 - Bioengineering and Digital Health
Forschungsfeld(er) Allergy
Enabling and Novel Technologies
PSP-Element(e) G-505490-001
G-554700-001
G-505400-001
G-503800-001
Förderungen Projekt DEAL
DOI 10.1038/s41467-022-35319-w
WOS ID 001028133600008
Scopus ID 85143784745
PubMed ID 36513651
Erfassungsdatum 2022-12-20
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