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

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

Nature communications (2024-01-30)
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, Ye H Oo
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.

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