Low numbers of cytokine transcripts drive inflammatory skin diseases by initiating amplification cascades in localized epidermal clusters
Low numbers of cytokine transcripts drive inflammatory skin diseases by initiating amplification cascades in localized epidermal clusters
Abstract Abundant polyclonal T cells infiltrate chronic inflammatory diseases and characterization of these cells is needed to distinguish disease-driving from bystander immune cells. Here, we investigated 52,000 human cutaneous transcriptomes of non-communicable inflammatory skin diseases (ncISD) using spatial transcriptomics. Despite the expected T cell infiltration, we observed only 1-10 pathogenic T cell cytokine per skin section. Cytokine expression was limited to lesional skin and presented in a disease-specific pattern. In fact, we identified responder signatures in direct proximity of cytokines, and showed that single cytokine transcripts initiate amplification cascades of thousands of specific responder transcripts forming localized epidermal clusters. Thus, within the abundant and polyclonal T cell infiltrates of ncISD, only a few T cells drive disease by initiating an inflammatory amplification cascade in their local microenvironment.
Thomas J.、Garzorz-Stark N.、Menden M.P.、Eyerich K K.、Sch?bitz A.、Farnoud A.、Pilz A.C.、Bhalla N.、Biedermann T.、Schmidt-Weber C.B.、Stahle M.、Theis F.、Jargosch M.、Scala E.、Eyerich S.、Mubarak M.、Hillig C.
Center for Allergy and Environment (ZAUM), Technical University and Helmholtz Center MunichDivision of Dermatology and Venereology, Department of Medicine Solna, and Center for Molecular Medicine, Karolinska Institutet||Department of Dermatology and Allergy, Technical University of MunichInstitute of Computational Biology, Helmholtz Zentrum M¨1nchen - German Research Centre for Environmental Health||Department of Biology, Ludwig-Maximilians University||German Center for Diabetes Research (DZD e.V.)Division of Dermatology and Venereology, Department of Medicine Solna, and Center for Molecular Medicine, Karolinska Institutet||Department of Dermatology and Allergy, Technical University of Munich||Department of Dermatology and Venereology, Unit of Dermatology, Karolinska University HospitalDivision of Dermatology and Venereology, Department of Medicine Solna, and Center for Molecular Medicine, Karolinska InstitutetInstitute of Computational Biology, Helmholtz Zentrum M¨1nchen - German Research Centre for Environmental HealthDepartment of Dermatology and Allergy, Technical University of MunichDepartment of Gene Technology, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of TechnologyDepartment of Dermatology and Allergy, Technical University of MunichCenter for Allergy and Environment (ZAUM), Technical University and Helmholtz Center MunichDivision of Dermatology and Venereology, Department of Medicine Solna, and Center for Molecular Medicine, Karolinska InstitutetInstitute of Computational Biology, Helmholtz Zentrum M¨1nchen - German Research Centre for Environmental HealthCenter for Allergy and Environment (ZAUM), Technical University and Helmholtz Center Munich||Department of Dermatology and Allergy, Technical University of MunichDivision of Dermatology and Venereology, Department of Medicine Solna, and Center for Molecular Medicine, Karolinska InstitutetCenter for Allergy and Environment (ZAUM), Technical University and Helmholtz Center MunichCenter for Allergy and Environment (ZAUM), Technical University and Helmholtz Center MunichInstitute of Computational Biology, Helmholtz Zentrum M¨1nchen - German Research Centre for Environmental Health
皮肤病学、性病学基础医学分子生物学
spatial transcriptomicschronic inflammatory skin diseasecytokinesskinpsoriasislichenatopic dermatitis
Thomas J.,Garzorz-Stark N.,Menden M.P.,Eyerich K K.,Sch?bitz A.,Farnoud A.,Pilz A.C.,Bhalla N.,Biedermann T.,Schmidt-Weber C.B.,Stahle M.,Theis F.,Jargosch M.,Scala E.,Eyerich S.,Mubarak M.,Hillig C..Low numbers of cytokine transcripts drive inflammatory skin diseases by initiating amplification cascades in localized epidermal clusters[EB/OL].(2025-03-28)[2025-06-03].https://www.biorxiv.org/content/10.1101/2021.06.10.447894.点此复制
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