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Spatial transcriptomics landscape of lesions from non-communicable inflammatory skin diseases
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 tra...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9747967/ https://www.ncbi.nlm.nih.gov/pubmed/36513651 http://dx.doi.org/10.1038/s41467-022-35319-w |
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author | 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. Garzorz-Stark, N. Eyerich, K. Menden, M. P. Eyerich, S. |
author_facet | 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. Garzorz-Stark, N. Eyerich, K. Menden, M. P. Eyerich, S. |
author_sort | Schäbitz, A. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9747967 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-97479672022-12-15 Spatial transcriptomics landscape of lesions from non-communicable inflammatory skin diseases 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. Garzorz-Stark, N. Eyerich, K. Menden, M. P. Eyerich, S. Nat Commun Article 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. Nature Publishing Group UK 2022-12-13 /pmc/articles/PMC9747967/ /pubmed/36513651 http://dx.doi.org/10.1038/s41467-022-35319-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article 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. Garzorz-Stark, N. Eyerich, K. Menden, M. P. Eyerich, S. Spatial transcriptomics landscape of lesions from non-communicable inflammatory skin diseases |
title | Spatial transcriptomics landscape of lesions from non-communicable inflammatory skin diseases |
title_full | Spatial transcriptomics landscape of lesions from non-communicable inflammatory skin diseases |
title_fullStr | Spatial transcriptomics landscape of lesions from non-communicable inflammatory skin diseases |
title_full_unstemmed | Spatial transcriptomics landscape of lesions from non-communicable inflammatory skin diseases |
title_short | Spatial transcriptomics landscape of lesions from non-communicable inflammatory skin diseases |
title_sort | spatial transcriptomics landscape of lesions from non-communicable inflammatory skin diseases |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9747967/ https://www.ncbi.nlm.nih.gov/pubmed/36513651 http://dx.doi.org/10.1038/s41467-022-35319-w |
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