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

A. Schäbitz, C. Hillig, M. Mubarak, M. Jargosch, A. Farnoud, E. Scala, N. Kurzen, A. C. Pilz, N. Bhalla, J. Thomas, M. Stahle, T. Biedermann, C. B. Schmidt-Weber, F. Theis, N. Garzorz-Stark, K. Eyerich, M. P. Menden and S. Eyerich ()
Additional contact information
A. Schäbitz: Karolinska Institutet
C. Hillig: Institute of Computational Biology, Helmholtz Zentrum München—German Research Centre for Environmental Health
M. Mubarak: Technical University and Helmholtz Center Munich
M. Jargosch: Technical University and Helmholtz Center Munich
A. Farnoud: Institute of Computational Biology, Helmholtz Zentrum München—German Research Centre for Environmental Health
E. Scala: Karolinska Institutet
N. Kurzen: Technical University and Helmholtz Center Munich
A. C. Pilz: Technical University of Munich
N. Bhalla: Biotechnology and Health, KTH Royal Institute of Technology
J. Thomas: Technical University and Helmholtz Center Munich
M. Stahle: Karolinska Institutet
T. Biedermann: Technical University of Munich
C. B. Schmidt-Weber: Technical University and Helmholtz Center Munich
F. Theis: Institute of Computational Biology, Helmholtz Zentrum München—German Research Centre for Environmental Health
N. Garzorz-Stark: Karolinska Institutet
K. Eyerich: Karolinska Institutet
M. P. Menden: Institute of Computational Biology, Helmholtz Zentrum München—German Research Centre for Environmental Health
S. Eyerich: Technical University and Helmholtz Center Munich

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35319-w

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DOI: 10.1038/s41467-022-35319-w

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