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Final Program


Final Program

Autoimmune Diseases

Th123 - The Immune Profile of Circulating Autoreactive CD4 T Cells Is Imprinted Through Tissue Activation During Autoimmune Liver Diseases

Thursday, June 26, 2025
7:30am - 7:45pm East Coast USA Time
  • TG

    Thomas Guinebretière, MSc

    PhD candidate
    Center for Research in Transplantation and Translational Immunology (CR2Ti)
    Nantes, Pays de la Loire, France

  • AC

    Anaïs Cardon

    Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France

  • CD

    Chuang Dong

    Aix Marseille Université, CNRS, INSERM, Centre d’Immunologie de Marseille-Luminy, CIML, Marseille, France

  • LG

    Laurine Gil

    Aix Marseille Université, CNRS, INSERM, Centre d’Immunologie de Marseille-Luminy, CIML, Marseille, France
    Marseille, Provence-Alpes-Cote d'Azur, France

  • SA

    Sakina Ado

    Aix Marseille Université, CNRS, INSERM, Centre d’Immunologie de Marseille-Luminy, CIML, Marseille, France

  • PG

    Pierre-Jean Gavlovsky

    Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France

  • MB

    Martin Braud

    Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France

  • RD

    Richard Danger, Ph.D.

    post-doctorate
    Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France
    Nantes, Pays de la Loire, France

  • CS

    Christoph Schultheiß

    Laboratory of Translational Immuno-Oncology, Department of Biomedicine, University and University Hospital Basel, Division of Oncology, University Hospital Basel, Basel, Switzerland

  • AD

    Aurélie Doméné

    Nantes Université, CHU Nantes, CNRS, Inserm, BioCore, US16, SFR Bonamy, F 44000 Nantes, France

  • PP

    Perrine Paul-Gilloteaux

    Nantes Université, CHU Nantes, CNRS, Inserm, BioCore, US16, SFR Bonamy, F 44000 Nantes, France

  • CC

    Caroline Chevalier

    Centre d'Investigation Clinique IMAD, CHU Nantes, Nantes, France

  • LB

    Laura Bernier

    Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France

  • JJ

    Jean-Paul Judor

    Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France

  • CF

    Cynthia Fourgeux, Ph.D.

    Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France
    Nantes, Pays de la Loire, France

  • AI

    Astrid Imbert

    Service Hepato-gastro-entérologie et Assistance Nutritionnelle, CHU Nantes, Nantes, France

  • MK

    Marion Khaldi

    Service Hepato-gastro-entérologie et Assistance Nutritionnelle, CHU Nantes, Nantes, France

  • EB

    Edouard Bardou-Jacquet

    CHU Rennes, Service des maladies du foie, Université Rennes, INSERM, INRAE, Institut NUMECAN, Rennes, France

  • LE

    Laure Elkrief

    CHRU Tours, Service Hépato-Gastroentérologie, Tours, France

  • AL

    Adrien Lannes

    CHU Angers, Service Hépato-Gastroentérologie et Oncologie Digestive, Université d'Angers, Laboratoire HIFIH, UPRES EA3859, SFR 4208, Angers, France

  • CS

    Christine Silvain

    CHU Poitiers, Service Hépato-Gastroentérologie, Poitiers, France

  • MS

    Matthieu Schnee

    CHD Vendée-La Roche sur Yon, Service Hépato-Gastroentérologie, F- 85000, la Roche sur Yon, France

  • FT

    Florence Tanne

    CHU Brest, Service Hépato-Gastroentérologie, Brest, France

  • FV

    Fabienne Vavasseur

    Centre d'Investigation Clinique IMAD, CHU Nantes, Nantes, France

  • LB

    Lucas Brusselle

    Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France

  • SB

    Sophie Brouard, PhD

    DR1 - Team leader
    Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France
    Nantes, Pays de la Loire, France

  • WK

    William W. Kwok, PhD

    Center for Translational Immunology, Benaroya Research Institute, Seattle, WA 98101, USA
    Seattle, Washington, United States

  • JM

    Jean-François Mosnier, M.D

    Service Anatomie et Cytologie Pathologiques, CHU Nantes, Nantes, France
    Nantes, Pays de la Loire, France

  • AL

    Ansgar W. Lohse

    First Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

  • JP

    Jeremie Poschmann, phd

    Prinicpal Investigator
    Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France
    Nantes, Pays de la Loire, France

  • MB

    Mascha Binder

    Laboratory of Translational Immuno-Oncology, Department of Biomedicine, University and University Hospital Basel, Division of Oncology, University Hospital Basel, Basel, Switzerland

  • JG

    Jérôme Gournay, M.D

    Service Hepato-gastro-entérologie et Assistance Nutritionnelle, CHU Nantes, Nantes, France
    Nantes, Pays de la Loire, France

  • SC

    Sophie Conchon

    Researcher PhD
    Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France
    Nantes, Pays de la Loire, France

  • PM

    Pierre Milpied, PhD

    Aix Marseille Université, CNRS, INSERM, Centre d’Immunologie de Marseille-Luminy, CIML, Marseille, France
    Marseille, Provence-Alpes-Cote d'Azur, France

  • AR

    Amédée Renand, PhD

    Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France
    Nantes, Pays de la Loire, France

Abstract Text:

Purpose: Autoimmune liver diseases (AILD) are immune-mediated disorders with CD4 T cell dysregulation, but the link between circulating self-antigen-specific CD4 T cells and the targeted tissue is still unclear. We hypothesized that circulating self-antigen-specific CD4 T cells contain dominant hepatic CD4 T cell clonotypes and represent liver-derived autoreactive CD4 T cells.

Methods: Self-antigen-specific CD4 T cells were isolated using CD154 upregulation following peptide stimulation, or with synthetized Sepsecs-peptide-loaded fluorescent-labeled MHCII-tetramers. Single-cell RNA-sequencing and TCR-sequencing were performed to investigate autoreactive CD4 T cell transcriptomic profile and clonotypes. A mouse model based on inducible expression of hepatocellular model antigen was designed to study the initiation and immuno-regulation of local antigen-specific immune response in the liver.

Results: Circulating self-antigen-specific CD4 T cells from AILD patients exhibit a specific B-helper and immuno-exhausted transcriptional profile, which is conserved for different autoantigens but distinct from foreign antigen specificities. In the blood, the PD-1+TIGIT+HLA-DR+ CD4 T cell subset shows a similar transcriptional signature to self-antigen-specific CD4 T cells and tissue-resident T cells, and contains highly expanded clones in the liver. In the mouse model, antigen-specific CD4 T cells acquire an immuno-exhausted transcriptional profile following their accumulation in the liver after local antigen reactivity, which is controlled by the immune checkpoint molecules PD-1 and CTLA-4.

Conclusion: Our findings reveal that autoreactive CD4 T cells in the blood of AILD patients may be imprinted by chronic self-antigen stimulation in the liver environment. Thus, deciphering circulating PD-1+TIGIT+HLA-DR+ CD4 T cells could provide autoimmune biomarkers and therapies.