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

Publié dans: Nat Commun 2025 Jan; 16(1): 1161

Auteurs: Cardon A, Guinebretière T, Dong C, Gil L, Ado S, Gavlovsky PJ, Braud M, Danger R, Schultheiß C, Doméné A, Paul-Gilloteaux P, Chevalier C, Bernier L, Judor JP, Fourgeux C, Imbert A, Khaldi M, Bardou-Jacquet E, Elkrief L, Lannes A, Silvain C, Schnee M, Tanne F, Vavasseur F, Brusselle L, Brouard S, Kwok WW, Mosnier JF, Lohse AW, Poschmann J, Binder M, Gournay J, Conchon S, Milpied P, Renand A

Résumé

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.

Lien vers Pubmed [PMID] – 39880819

Lien vers le DOI – 10.1038/s41467-025-56363-2