Overview

• Dendritic cells coordinate lamellipodial protrusions at the front with a central actin assembly to exert pushing forces in three-dimensional tissues.
• Central actin structures generate sideways pressure that displaces collagen fibers and opens narrow passages without enzymatic digestion.
• In the absence of DOCK8, cells cannot form central actin cores, become lodged in constrictions, produce uncontrolled front protrusions, and undergo fragmentation.
• Researchers link the failure of this push-based navigation to the cellular basis of a rare immunodeficiency marked by recurring viral infections and skin lesions.
• The peer-reviewed work in Nature Immunology sets a new mechanistic framework for immune cell migration and suggests targets for DOCK8-deficiency therapies.