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Single cell profiling of circulating autoreactive CD4 T cells from patients with autoimmune liver diseases suggests tissue imprinting

Author

Listed:
  • Anaïs Cardon

    (UMR 1064)

  • Thomas Guinebretière

    (UMR 1064)

  • Chuang Dong

    (CIML)

  • Laurine Gil

    (CIML)

  • Sakina Ado

    (CIML)

  • Pierre-jean Gavlovsky

    (UMR 1064)

  • Martin Braud

    (UMR 1064)

  • Richard Danger

    (UMR 1064)

  • Christoph Schultheiß

    (University Hospital Basel)

  • Aurélie Doméné

    (SFR Bonamy)

  • Perrine Paul-Gilloteaux

    (SFR Bonamy)

  • Caroline Chevalier

    (CHU Nantes)

  • Laura Bernier

    (UMR 1064)

  • Jean-Paul Judor

    (UMR 1064)

  • Cynthia Fourgeux

    (UMR 1064)

  • Astrid Imbert

    (CHU Nantes)

  • Marion Khaldi

    (CHU Nantes
    CHU Nantes)

  • Edouard Bardou-Jacquet

    (Institut NUMECAN)

  • Laure Elkrief

    (Service Hépato-Gastroentérologie)

  • Adrien Lannes

    (UPRES EA3859, SFR 4208)

  • Christine Silvain

    (Service Hépato-Gastroentérologie)

  • Matthieu Schnee

    (Service Hépato-Gastroentérologie, F- 85000)

  • Florence Tanne

    (Service Hépato-Gastroentérologie)

  • Fabienne Vavasseur

    (CHU Nantes)

  • Lucas Brusselle

    (UMR 1064)

  • Sophie Brouard

    (UMR 1064)

  • William W. Kwok

    (Benaroya Research Institute)

  • Jean-François Mosnier

    (UMR 1064
    CHU Nantes)

  • Ansgar W. Lohse

    (University Medical Center Hamburg-Eppendorf)

  • Jeremie Poschmann

    (UMR 1064)

  • Mascha Binder

    (University Hospital Basel)

  • Jérôme Gournay

    (UMR 1064
    CHU Nantes
    CHU Nantes)

  • Sophie Conchon

    (UMR 1064)

  • Pierre Milpied

    (CIML)

  • Amédée Renand

    (UMR 1064)

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.

Suggested Citation

  • Anaïs Cardon & Thomas Guinebretière & Chuang Dong & Laurine Gil & Sakina Ado & Pierre-jean Gavlovsky & Martin Braud & Richard Danger & Christoph Schultheiß & Aurélie Doméné & Perrine Paul-Gilloteaux &, 2025. "Single cell profiling of circulating autoreactive CD4 T cells from patients with autoimmune liver diseases suggests tissue imprinting," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56363-2
    DOI: 10.1038/s41467-025-56363-2
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    References listed on IDEAS

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