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Expression of E-cadherin by CD8+ T cells promotes their invasion into biliary epithelial cells

Author

Listed:
  • Scott P. Davies

    (University of Birmingham
    University of Birmingham and University Hospitals Birmingham NHS Foundation Trust
    University Hospitals Birmingham NHS Foundation Trust
    European Reference Network on Hepatological Diseases (ERN Rare-Liver))

  • Vincenzo Ronca

    (University of Birmingham
    University of Birmingham and University Hospitals Birmingham NHS Foundation Trust
    European Reference Network on Hepatological Diseases (ERN Rare-Liver))

  • Grace E. Wootton

    (University of Birmingham
    University of Birmingham and University Hospitals Birmingham NHS Foundation Trust
    University Hospitals Birmingham NHS Foundation Trust
    European Reference Network on Hepatological Diseases (ERN Rare-Liver))

  • Natalia M. Krajewska

    (University of Birmingham
    University of Birmingham and University Hospitals Birmingham NHS Foundation Trust)

  • Amber G. Bozward

    (University of Birmingham
    University of Birmingham and University Hospitals Birmingham NHS Foundation Trust
    University Hospitals Birmingham NHS Foundation Trust
    European Reference Network on Hepatological Diseases (ERN Rare-Liver))

  • Rémi Fiancette

    (University of Birmingham
    University of Birmingham and University Hospitals Birmingham NHS Foundation Trust
    University Hospitals Birmingham NHS Foundation Trust)

  • Daniel A. Patten

    (University of Birmingham
    University of Birmingham and University Hospitals Birmingham NHS Foundation Trust
    University Hospitals Birmingham NHS Foundation Trust)

  • Katharina Yankouskaya

    (University of Birmingham
    University of Birmingham and University Hospitals Birmingham NHS Foundation Trust)

  • Gary M. Reynolds

    (University of Birmingham
    University of Birmingham and University Hospitals Birmingham NHS Foundation Trust)

  • Sofia Pat

    (University of Birmingham
    University of Birmingham and University Hospitals Birmingham NHS Foundation Trust)

  • Daniel C. Osei-Bordom

    (University of Birmingham
    University of Birmingham and University Hospitals Birmingham NHS Foundation Trust)

  • Naomi Richardson

    (University of Birmingham
    University of Birmingham and University Hospitals Birmingham NHS Foundation Trust
    University Hospitals Birmingham NHS Foundation Trust
    European Reference Network on Hepatological Diseases (ERN Rare-Liver))

  • Liam M. Grover

    (University of Birmingham and University Hospitals Birmingham NHS Foundation Trust
    University of Birmingham
    University of Birmingham)

  • Christopher J. Weston

    (University of Birmingham
    University of Birmingham and University Hospitals Birmingham NHS Foundation Trust
    University Hospitals Birmingham NHS Foundation Trust)

  • Ye H. Oo

    (University of Birmingham
    University of Birmingham and University Hospitals Birmingham NHS Foundation Trust
    University Hospitals Birmingham NHS Foundation Trust
    European Reference Network on Hepatological Diseases (ERN Rare-Liver))

Abstract

The presence of CD8+ T cells in the cytoplasm of biliary epithelial cells (BEC) has been correlated with biliary damage associated with primary biliary cholangitis (PBC). Here, we characterise the mechanism of CD8+ T cell invasion into BEC. CD8+ T cells observed within BEC were large, eccentric, and expressed E-cadherin, CD103 and CD69. They were also not contained within secondary vesicles. Internalisation required cytoskeletal rearrangements which facilitated contact with BEC. Internalised CD8+ T cells were observed in both non-cirrhotic and cirrhotic diseased liver tissues but enriched in PBC patients, both during active disease and at the time of transplantation. E-cadherin expression by CD8+ T cells correlated with frequency of internalisation of these cells into BEC. E-cadherin+ CD8+ T cells formed β-catenin-associated interactions with BEC, were larger than E-cadherin- CD8+ T cells and invaded into BEC more frequently. Overall, we unveil a distinct cell-in-cell structure process in the liver detailing the invasion of E-cadherin+ CD103+ CD69+ CD8+ T cells into BEC.

Suggested Citation

  • Scott P. Davies & Vincenzo Ronca & Grace E. Wootton & Natalia M. Krajewska & Amber G. Bozward & Rémi Fiancette & Daniel A. Patten & Katharina Yankouskaya & Gary M. Reynolds & Sofia Pat & Daniel C. Ose, 2024. "Expression of E-cadherin by CD8+ T cells promotes their invasion into biliary epithelial cells," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44910-2
    DOI: 10.1038/s41467-024-44910-2
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