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

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. Osei-Bordom, Naomi Richardson, Liam M. Grover, Christopher J. Weston and Ye H. Oo ()
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Scott P. Davies: University of Birmingham
Vincenzo Ronca: University of Birmingham
Grace E. Wootton: University of Birmingham
Natalia M. Krajewska: University of Birmingham
Amber G. Bozward: University of Birmingham
Rémi Fiancette: University of Birmingham
Daniel A. Patten: University of Birmingham
Katharina Yankouskaya: University of Birmingham
Gary M. Reynolds: University of Birmingham
Sofia Pat: University of Birmingham
Daniel C. Osei-Bordom: University of Birmingham
Naomi Richardson: University of Birmingham
Liam M. Grover: University of Birmingham and University Hospitals Birmingham NHS Foundation Trust
Christopher J. Weston: University of Birmingham
Ye H. Oo: University of Birmingham

Nature Communications, 2024, vol. 15, issue 1, 1-22

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-44910-2

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