Single cell profiling of circulating autoreactive CD4 T cells from patients with autoimmune liver diseases suggests tissue imprinting
Abstract Autoimmune liver diseases (AILD) involve dysregulated CD4 T cell responses against liver self-antigens, but how these autoreactive T cells relate to liver tissue pathology remains unclear. Here we perform single-cell transcriptomic and T cell receptor analyses of circulating, self-antigen-s...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56363-2 |
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| author | Anaïs Cardon Thomas Guinebretière Chuang Dong Laurine Gil Sakina Ado Pierre-jean Gavlovsky Martin Braud Richard Danger Christoph Schultheiß Aurélie Doméné Perrine Paul-Gilloteaux Caroline Chevalier Laura Bernier Jean-Paul Judor Cynthia Fourgeux Astrid Imbert Marion Khaldi Edouard Bardou-Jacquet Laure Elkrief Adrien Lannes Christine Silvain Matthieu Schnee Florence Tanne Fabienne Vavasseur Lucas Brusselle Sophie Brouard William W. Kwok Jean-François Mosnier Ansgar W. Lohse Jeremie Poschmann Mascha Binder Jérôme Gournay Sophie Conchon Pierre Milpied Amédée Renand |
| author_facet | Anaïs Cardon Thomas Guinebretière Chuang Dong Laurine Gil Sakina Ado Pierre-jean Gavlovsky Martin Braud Richard Danger Christoph Schultheiß Aurélie Doméné Perrine Paul-Gilloteaux Caroline Chevalier Laura Bernier Jean-Paul Judor Cynthia Fourgeux Astrid Imbert Marion Khaldi Edouard Bardou-Jacquet Laure Elkrief Adrien Lannes Christine Silvain Matthieu Schnee Florence Tanne Fabienne Vavasseur Lucas Brusselle Sophie Brouard William W. Kwok Jean-François Mosnier Ansgar W. Lohse Jeremie Poschmann Mascha Binder Jérôme Gournay Sophie Conchon Pierre Milpied Amédée Renand |
| author_sort | Anaïs Cardon |
| collection | DOAJ |
| description | Abstract Autoimmune liver diseases (AILD) involve dysregulated CD4 T cell responses against liver self-antigens, but how these autoreactive T cells relate to liver tissue pathology remains unclear. Here we perform single-cell transcriptomic and T cell receptor analyses of circulating, self-antigen-specific CD4 T cells from patients with AILD and identify a subset of liver-autoreactive CD4 T cells with a distinct B-helper transcriptional profile characterized by PD-1, TIGIT and HLA-DR expression. These cells share clonal relationships with expanded intrahepatic T cells and exhibit transcriptional signatures overlapping with tissue-resident T cells in chronically inflamed environments. Using a mouse model, we demonstrate that, following antigen recognition in the liver, CD4 T cells acquire an exhausted phenotype, play a crucial role in liver damage, and are controlled by immune checkpoint pathways. Our findings thus suggest that circulating autoreactive CD4 T cells in AILD are imprinted by chronic antigen exposure to promote liver inflammation, thereby serving as a potential target for developing biomarkers and therapies for AILD. |
| format | Article |
| id | doaj-art-ad0927309fac445595b589b0734522f8 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-ad0927309fac445595b589b0734522f82025-02-02T12:32:42ZengNature PortfolioNature Communications2041-17232025-01-0116112010.1038/s41467-025-56363-2Single cell profiling of circulating autoreactive CD4 T cells from patients with autoimmune liver diseases suggests tissue imprintingAnaïs Cardon0Thomas Guinebretière1Chuang Dong2Laurine Gil3Sakina Ado4Pierre-jean Gavlovsky5Martin Braud6Richard Danger7Christoph Schultheiß8Aurélie Doméné9Perrine Paul-Gilloteaux10Caroline Chevalier11Laura Bernier12Jean-Paul Judor13Cynthia Fourgeux14Astrid Imbert15Marion Khaldi16Edouard Bardou-Jacquet17Laure Elkrief18Adrien Lannes19Christine Silvain20Matthieu Schnee21Florence Tanne22Fabienne Vavasseur23Lucas Brusselle24Sophie Brouard25William W. Kwok26Jean-François Mosnier27Ansgar W. Lohse28Jeremie Poschmann29Mascha Binder30Jérôme Gournay31Sophie Conchon32Pierre Milpied33Amédée Renand34Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064Aix Marseille Université, CNRS, INSERM, Centre d’Immunologie de Marseille-Luminy, CIMLAix Marseille Université, CNRS, INSERM, Centre d’Immunologie de Marseille-Luminy, CIMLAix Marseille Université, CNRS, INSERM, Centre d’Immunologie de Marseille-Luminy, CIMLNantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064Laboratory of Translational Immuno-Oncology, Department of Biomedicine, University and University Hospital Basel, Division of Oncology, University Hospital BaselNantes Université, CHU Nantes, CNRS, Inserm, BioCore, US16, SFR BonamyNantes Université, CHU Nantes, CNRS, Inserm, BioCore, US16, SFR BonamyCentre d’Investigation Clinique IMAD, CHU NantesNantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064Service Hepato-gastro-entérologie et Assistance Nutritionnelle, CHU NantesService Hepato-gastro-entérologie et Assistance Nutritionnelle, CHU NantesCHU Rennes, Service des maladies du foie, Université Rennes, INSERM, INRAE, Institut NUMECANCHRU Tours, Service Hépato-GastroentérologieCHU Angers, Service Hépato-Gastroentérologie et Oncologie Digestive, Université d’Angers, Laboratoire HIFIH, UPRES EA3859, SFR 4208CHU Poitiers, Service Hépato-GastroentérologieCHD Vendée-La Roche sur Yon, Service Hépato-Gastroentérologie, F- 85000CHU Brest, Service Hépato-GastroentérologieCentre d’Investigation Clinique IMAD, CHU NantesNantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064Center for Translational Immunology, Benaroya Research InstituteNantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064First Department of Medicine, University Medical Center Hamburg-EppendorfNantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064Laboratory of Translational Immuno-Oncology, Department of Biomedicine, University and University Hospital Basel, Division of Oncology, University Hospital BaselNantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064Aix Marseille Université, CNRS, INSERM, Centre d’Immunologie de Marseille-Luminy, CIMLNantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064Abstract Autoimmune liver diseases (AILD) involve dysregulated CD4 T cell responses against liver self-antigens, but how these autoreactive T cells relate to liver tissue pathology remains unclear. Here we perform single-cell transcriptomic and T cell receptor analyses of circulating, self-antigen-specific CD4 T cells from patients with AILD and identify a subset of liver-autoreactive CD4 T cells with a distinct B-helper transcriptional profile characterized by PD-1, TIGIT and HLA-DR expression. These cells share clonal relationships with expanded intrahepatic T cells and exhibit transcriptional signatures overlapping with tissue-resident T cells in chronically inflamed environments. Using a mouse model, we demonstrate that, following antigen recognition in the liver, CD4 T cells acquire an exhausted phenotype, play a crucial role in liver damage, and are controlled by immune checkpoint pathways. Our findings thus suggest that circulating autoreactive CD4 T cells in AILD are imprinted by chronic antigen exposure to promote liver inflammation, thereby serving as a potential target for developing biomarkers and therapies for AILD.https://doi.org/10.1038/s41467-025-56363-2 |
| spellingShingle | Anaïs Cardon Thomas Guinebretière Chuang Dong Laurine Gil Sakina Ado Pierre-jean Gavlovsky Martin Braud Richard Danger Christoph Schultheiß Aurélie Doméné Perrine Paul-Gilloteaux Caroline Chevalier Laura Bernier Jean-Paul Judor Cynthia Fourgeux Astrid Imbert Marion Khaldi Edouard Bardou-Jacquet Laure Elkrief Adrien Lannes Christine Silvain Matthieu Schnee Florence Tanne Fabienne Vavasseur Lucas Brusselle Sophie Brouard William W. Kwok Jean-François Mosnier Ansgar W. Lohse Jeremie Poschmann Mascha Binder Jérôme Gournay Sophie Conchon Pierre Milpied Amédée Renand Single cell profiling of circulating autoreactive CD4 T cells from patients with autoimmune liver diseases suggests tissue imprinting Nature Communications |
| title | Single cell profiling of circulating autoreactive CD4 T cells from patients with autoimmune liver diseases suggests tissue imprinting |
| title_full | Single cell profiling of circulating autoreactive CD4 T cells from patients with autoimmune liver diseases suggests tissue imprinting |
| title_fullStr | Single cell profiling of circulating autoreactive CD4 T cells from patients with autoimmune liver diseases suggests tissue imprinting |
| title_full_unstemmed | Single cell profiling of circulating autoreactive CD4 T cells from patients with autoimmune liver diseases suggests tissue imprinting |
| title_short | Single cell profiling of circulating autoreactive CD4 T cells from patients with autoimmune liver diseases suggests tissue imprinting |
| title_sort | single cell profiling of circulating autoreactive cd4 t cells from patients with autoimmune liver diseases suggests tissue imprinting |
| url | https://doi.org/10.1038/s41467-025-56363-2 |
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