# Expansion of CD103+CD69+CD8+ cytotoxic liver tissue resident memory T cells and inflammatory monocytes in advanced biliary atresia

## TL;DR

This study finds that specific immune cells in the liver are more active in children with biliary atresia, suggesting they may contribute to liver damage and could be targets for new therapies.

## Contribution

The study identifies expanded CD103+CD69+CD8+ T cells and inflammatory monocytes in biliary atresia, linking them to tissue destruction and potential therapeutic targets.

## Key findings

- CD103+CD69+CD8+ Trm cells and CD14+CD16+ monocytes are significantly increased in biliary atresia compared to controls.
- T cells in BA show elevated CD103, CD69, CD39 expression and produce more TNF-α and Granzyme-B.
- Cell contact with monocytes in vitro reproduces the elevated T cell activity observed in BA.

## Abstract

The pathogenesis of biliary atresia (BA) is unclear to date and no therapies targeting immune regulatory pathways exist. Here we characterized potent effector liver tissue resident memory CD8+ T cells (Trm) and monocytic cells in children with advanced BA and an age-matched control group to gain insight into BA pathogenesis and immunologic regulation.

Liver explants from 18 children with biliary atresia and 10 with metabolic disease and normal histology were analyzed ex vivo by multicolor flow-cytometry and immunohistochemistry. Cytokines and cytotoxic mediators were quantified by intracellular staining and bead-based arrays in culture supernatant.

The frequency of CD103+CD69+CD8+ Trm cells and CD14+CD16+ monocytes was significantly higher in BA than in the control group. In BA, T cells showed elevated expression of CD103, CD69, CD39 and production of TNF-α and Granzyme-B ex vivo, which could be reproduced in vitro by allowing cell-contact with monocytes.

Cytotoxic CD8+ Trm cells and intrahepatic monocytes might contribute to tissue destruction in BA. Therapies targeting Trm cells or the TNF-α signaling pathway could be explored to delay progression to cirrhosis in BA.