Calcium dynamics of skin-resident macrophages during homeostasis and tissue injury

Immune cells depend on rapid changes in intracellular calcium activity to modulate cell function. Skin contains diverse immune cell types and is critically dependent on calcium signaling for homeostasis and repair, yet the dynamics and functions of calcium in skin immune cells remain poorly understood. Here, we characterize calcium activity in Langerhans cells, skin-resident macrophages responsible for surveillance and clearance of cellular debris after tissue damage. Langerhans cells reside in the epidermis and extend dynamic dendrites in close proximity to adjacent keratinocytes and somatosensory peripheral axons. We find that homeostatic Langerhans cells exhibit spontaneous and transient changes in calcium activity, with calcium flux occurring primarily in the cell body and rarely in the dendrites. Triggering somatosensory axon degeneration increases the frequency of calcium activity in Langerhans cell dendrites. By contrast, we show that Langerhans cells exhibit a sustained increase in intracellular calcium following engulfment of damaged keratinocytes. Altering intracellular calcium activity leads to a decrease in engulfment efficiency of keratinocyte debris. Our findings demonstrate that Langerhans cells exhibit context-specific changes in calcium activity and highlight the utility of skin as an accessible model for imaging calcium dynamics in tissue-resident macrophages. SIGNIFICANCE STATEMENTO_LICalcium activity in immune cells is thought to regulate cell function, but studies focusing on tissue-resident macrophages are limited. C_LIO_LISkin-resident macrophages known as Langerhans cells exhibit rapid and transient changes in calcium activity in homeostatic conditions, which can change depending on the type of tissue injury inflicted. Pharmacological perturbation of calcium activity leads to a decrease in Langerhans cell engulfment. C_LIO_LIThese findings suggest calcium activity is important for tissue surveillance by Langerhans cells. C_LI