# Leukocyte-epithelial physical contacts mediate interstitial migration in vivo

## TL;DR

This study reveals how immune cells move through dense tissues by interacting physically with epithelial cells in live zebrafish.

## Contribution

The paper identifies specific physical and molecular mechanisms by which leukocytes navigate through epithelial tissues in vivo.

## Key findings

- Confining forces from epithelial cells trigger a mechanosensitive actin network in neutrophils.
- Leukocyte-epithelial contacts via integrin ɑE and cadherin generate traction for migration.
- These interactions enable neutrophils to dilate and move through dense tissues.

## Abstract

Efficient immune cell migration requires physical interactions with surrounding tissues. While tissue matrix mechanics influence leukocyte motility, it is unknown how leukocytes exert pushing and pulling forces to traverse tightly adherent epithelial tissues, which comprise a majority of tissue volume in vivo. Here, we leverage the optical transparency of larval zebrafish to identify how physical interactions with epithelial cells regulate mechanisms of neutrophil force generation to navigate cell-dense tissues. Confining forces from epithelial cells induce a mechanosensitive central actin network, mediated by Cdc42 and WASP, which exerts expansile forces on surrounding cells to dilate a path for migration. In concert, direct cell-to-cell (leukocyte-epithelial) contacts, mediated by integrin ɑE binding to epithelial cadherin, generate tractional forces to enable forward motility. Together, our findings identify how physical interactions with surrounding epithelial cells regulate leukocyte motility through cell-dense tissues in vivo.