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

Schäbitz, A. (författare)
Karolinska Institutet
Hillig, C. (författare)
Institute of Computational Biology, Helmholtz Zentrum München—German Research Centre for Environmental Health, Ingolstädter Landstrasse 1, 85764, Neuherberg, Germany, Ingolstädter Landstrasse 1
Mubarak, M. (författare)
Karolinska Institutet
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Jargosch, M. (författare)
Center for Allergy and Environment (ZAUM), Technical University and Helmholtz Center Munich, Biedersteinerstrasse 29, 80802, Munich, Germany, Biedersteinerstrasse 29; Department of Dermatology and Allergy, Technical University of Munich, Biedersteinerstrasse 29, 80802, Munich, Germany, Biedersteinerstrasse 29
Farnoud, A. (författare)
Institute of Computational Biology, Helmholtz Zentrum München—German Research Centre for Environmental Health, Ingolstädter Landstrasse 1, 85764, Neuherberg, Germany, Ingolstädter Landstrasse 1
Scala, E. (författare)
Karolinska Institutet
Kurzen, N. (författare)
Center for Allergy and Environment (ZAUM), Technical University and Helmholtz Center Munich, Biedersteinerstrasse 29, 80802, Munich, Germany, Biedersteinerstrasse 29
Pilz, A. C. (författare)
Department of Dermatology and Allergy, Technical University of Munich, Biedersteinerstrasse 29, 80802, Munich, Germany, Biedersteinerstrasse 29; Department of Dermatology and Venerology, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Bhalla, Nayanika (författare)
KTH,Genteknologi
Thomas, J. (författare)
Center for Allergy and Environment (ZAUM), Technical University and Helmholtz Center Munich, Biedersteinerstrasse 29, 80802, Munich, Germany, Biedersteinerstrasse 29
Stahle, M. (författare)
Division of Dermatology and Venereology, Department of Medicine Solna, and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
Biedermann, T. (författare)
Department of Dermatology and Allergy, Technical University of Munich, Biedersteinerstrasse 29, 80802, Munich, Germany, Biedersteinerstrasse 29
Schmidt-Weber, C. B. (författare)
Center for Allergy and Environment (ZAUM), Technical University and Helmholtz Center Munich, Biedersteinerstrasse 29, 80802, Munich, Germany, Biedersteinerstrasse 29
Theis, F. (författare)
Institute of Computational Biology, Helmholtz Zentrum München—German Research Centre for Environmental Health, Ingolstädter Landstrasse 1, 85764, Neuherberg, Germany, Ingolstädter Landstrasse 1
Garzorz-Stark, N. (författare)
Division of Dermatology and Venereology, Department of Medicine Solna, and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Dermatology and Allergy, Technical University of Munich, Biedersteinerstrasse 29, 80802, Munich, Germany, Biedersteinerstrasse 29
Eyerich, K. (författare)
Karolinska Institutet
Menden, M. P. (författare)
Institute of Computational Biology, Helmholtz Zentrum München—German Research Centre for Environmental Health, Ingolstädter Landstrasse 1, 85764, Neuherberg, Germany, Ingolstädter Landstrasse 1; Department of Biology, Ludwig-Maximilians University, Goßhadernerstrasse 2, Martinsried, 82152, Germany, Goßhadernerstrasse 2; German Center for Diabetes Research (DZD e.V.), Ingolstädter Landstrasse 1, 85764, Neuherberg, Germany, Ingolstädter Landstrasse 1
Eyerich, S. (författare)
Center for Allergy and Environment (ZAUM), Technical University and Helmholtz Center Munich, Biedersteinerstrasse 29, 80802, Munich, Germany, Biedersteinerstrasse 29
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 (creator_code:org_t)
2022-12-13
2022
Engelska.
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
Relaterad länk:
https://doi.org/10.1...
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https://urn.kb.se/re...
https://doi.org/10.1...
http://kipublication...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)

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