Santos-Argumedo, L. | Search bioRxiv

bioRxiv2022

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 a4b7 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 and having consequences in cell signaling. Overall, we demonstrate that Myo1f has an essential role in the adhesion and migration in {gamma}{delta}T intraepithelial lymphocytes. SUMMARY STATEMENTThe adhesion and migration of {gamma}{delta}T intraepithelial lymphocytes are regulated by the motor protein Myosin 1f through controlling the expression of integrins and the chemokine receptor CCR9.

cell biology↗

bioRxiv2019

Myo1e modulates the recruitment of B cells to inguinal lymph nodes

The recruitment of leukocyte to high endothelium venules and their migration to the lymph nodes are critical steps to initiate an immune response. Cell migration is regulated by the actin cytoskeleton where myosins have a very import role. Myo1e is a long tail class I myosin highly expressed in B cells that not have been studied in the context of cell migration. By using an in vivo model, through the use of intravital microscopy, we demonstrated the relevance of Myo1e in the adhesion and the migration of B cells in high endothelial venules. These observations were confirmed by in vitro experiments. We also registered a reduction in the expression of integrins and F-actin in the protrusion of B lymphocytes membrane. Deficiencies in vesicular trafficking can explain the decrease of integrins on the surface. Interestingly, Myo1e is associated with focal adhesion kinase (FAK). The lack of Myo1e affected the phosphorylation of FAK and AKT, and the activity of RAC-1, disturbing the FAK/PI3K/RAC-1 signaling pathway. Together, our results indicate critical participation of Myo1e in the mechanism of B cell migration.\n\nSummary statementMyo1e participate in the adhesion and migration in the high endothelial venules by regulation of integrins and the PI3K/FAK/RAC-1 signaling pathway.

immunology↗