Microtubules regulate tissue-level navigation in skin-resident macrophages

Immune cells rapidly respond to tissue damage through dynamic properties of the cytoskeleton. How microtubules control immune cell functions during injury responses remains poorly understood. Within skin, tissue-resident macrophages known as Langerhans cells use dynamic dendrites to surveil the epidermis for damage and migrate through a densely packed epithelium to wounds. Here, we used Langerhans cells within the adult zebrafish epidermis as a model to investigate roles of microtubules in immune cell tissue surveillance, phagocytosis and directed migration. We describe microtubule organization within Langerhans cells and show that depolymerizing the microtubule cytoskeleton alters dendrite morphology, debris engulfment and migration efficiency. We found that the microtubule organizing center positions adjacent to engulfed debris and that its position correlates with navigational pathfinding during tissue-level migration. Stabilizing microtubules inhibits Langerhans cell motility during directed cell migration by impairing navigation around cellular obstacles. Collectively, our work demonstrates requirements for microtubules in the dynamic actions of tissue-resident macrophages during epithelial surveillance and wound repair.