Clear Search sequence regions


  • antibodies (1)
  • autoantigens (6)
  • b cells (1)
  • cells hybrid (1)
  • chronic disease (1)
  • female (1)
  • humans (1)
  • lymphocyte (1)
  • man (1)
  • memory (6)
  • mice (3)
  • nephritis (6)
  • patients (1)
  • t lymphocytes (12)
  • Sizes of these terms reflect their relevance to your search.

    Immune-mediated nephritis is a leading cause of acute kidney injury and chronic kidney disease. While the role of B cells and antibodies has been extensively investigated in the past, the advent of immune-checkpoint inhibitors has led to a reappraisal of the role of T cells in renal immunology. However, it remains elusive how T cells with specificity for renal autoantigens are activated and participate in immune-mediated nephritis. Here, we followed the fate and function of pathogen-activated autoreactive CD8 T cells that are specific for a renal autoantigen. We demonstrate that recently activated splenic CD8 T cells developed a hybrid phenotype in the context of renal autoantigen cross-presentation, combining hallmarks of activation and T cell dysfunction. While circulating memory T cells rapidly disappeared, tissue-resident memory T cells emerged and persisted within the kidney, orchestrating immune-mediated nephritis. Notably, T cells infiltrating kidneys of patients with interstitial nephritis also expressed key markers of tissue residency. This study unveils how a tissue-specific immune response can dissociate from its systemic counterpart driving a compartmentalized immune response in the kidneys of mice and man. Consequently, targeting tissue-resident memory T cells emerges as a promising strategy to control immune-mediated kidney disease. © 2024. The Author(s).

    Citation

    Frederic Arnold, Laurence Kupferschmid, Philipp Weissenborn, Lukas Heldmann, Jonas F Hummel, Paulina Zareba, Sagar, Manuel Rogg, Christoph Schell, Yakup Tanriver. Tissue-resident memory T cells break tolerance to renal autoantigens and orchestrate immune-mediated nephritis. Cellular & molecular immunology. 2024 Sep;21(9):1066-1081

    Expand section icon Mesh Tags

    Expand section icon Substances


    PMID: 38961265

    View Full Text