Myo1f has an essential role in γδT intraepithelial lymphocyte adhesion and migration

gamma delta T intraepithelial lymphocyte represents up to 60% of the small intestine intraepithelial compartment. They are highly migrating cells and constantly interact with the epithelial cell layer and lamina propria cells. This migratory phenotype is related to the homeostasis of the small intestine, the control of bacterial and parasitic infections, and the epithelial shedding induced by LPS. Here, we demonstrate that Myo1f participates in the adhesion and migration of intraepithelial lymphocytes. Using long-tailed class I myosins KO mice, we identified the requirement of Myo1f for their migration to the small intestine intraepithelial compartment. The absence of Myo1f affects intraepithelial lymphocytes' homing due to reduced CCR9 and alpha 4 beta 7 surface expression. In vitro, we confirm that adhesion to integrin ligands and CCL25-dependent and independent migration of intraepithelial lymphocytes are Myo1f-dependent. Mechanistically, Myo1f deficiency prevents correct chemokine receptor and integrin polarization, leading to reduced tyrosine phosphorylation which could impact in signal transduction. Overall, we demonstrate that Myo1f has an essential role in the adhesion and migration in gamma delta T intraepithelial lymphocytes.

Automated summary

Gamma delta T intraepithelial lymphocytes account for up to 60% of the small intestine intraepithelial compartment. The adhesion and migration of these cells are dependent on the protein Myo1f. Myo1f deficiency leads to reduced surface expression of CCR9 and alpha 4 beta 7, affecting the homing of intraepithelial lymphocytes. In vitro experiments confirm that Myo1f is required for adhesion to integrin ligands and for CCL25-dependent and independent migration.