Rho-associated kinase regulates Langerhans cell morphology and responsiveness to tissue damage

Abstract

Skin is often the first physical barrier to encounter invading pathogens and physical damage. Damage to the skin must be resolved quickly and efficiently to maintain organ homeostasis. Epidermal-resident immune cells known as Langerhans cells use dendritic protrusions to dynamically surveil the skin microenvironment, which contains epithelial keratinocytes and somatosensory peripheral axons. The mechanisms governing Langerhans cell dendrite dynamics and responses to tissue damage are not well understood. Using skin explants from adult zebrafish, we show that Langerhans cells maintain normal surveillance activity following axonal degeneration and use their dynamic dendrites to engulf small axonal debris. By contrast, a ramified-to-rounded shape transition accommodates the engulfment of larger keratinocyte debris. We find that Langerhans cell dendrites are richly populated with actin and sensitive to a broad spectrum actin inhibitor. We further show that Rho-associated kinase (ROCK) inhibition leads to elongated dendrites, perturbed clearance of large debris, and reduced Langerhans cell migration to tissue-scale wounds. Altogether, our work describes the unique dynamics of Langerhans cells and involvement of the ROCK pathway in immune cell responses to damage of varying magnitude.