Manuscript from Pearl and Eric now online at MBoC!

Our paper from first-author Pearl Leon Guerrero and senior-author Eric Peterman is now accepted at Molecular Biology of the Cell. Details on the study below:

Immune cells integrate diverse signals to efficiently respond to infection or tissue damage. Among these signals are fluctuations in intracellular calcium, an important secondary messenger with roles in cell motility, T cell signaling, and phagocytosis. Monitoring and perturbing calcium activity in vivo presents unique challenges and, to date, only a handful of studies have investigated calcium activity in tissue-resident macrophages (TRMs) in their native context. Thus, developing an accessible animal model to study changes in calcium activity during TRM homeostasis and tissue damage responses would provide important insights into calcium requirements in immune cells.

In our paper, we used our previously established model of adult zebrafish scales to visualize skin TRMs known as Langerhans cells. The flat and transparent nature of the scale epidermis lends itself to superior imaging of Langerhans cells, including the assessment of cellular dendrite dynamics and phagocytosis of cellular debris in several injury paradigms. We used transgenic fish expressing the calcium indicator GCaMP to visualize calcium activity in Langerhans cells. While some requirements of calcium activity in Langerhans cells function have been examined, the real-time monitoring of calcium levels in these cells has not been previously reported. Our novel insights include: 1) the discovery that Langerhans cells exhibit spontaneous, transient changes in calcium levels during homeostasis; 2) that fluctuations in calcium most often occurred in the Langerhans cell body rather than in the dynamic dendrites and appeared unsynchronized across the epidermis; 3) that Langerhans cells exhibit distinct changes in calcium activity in response to axon degeneration versus single keratinocyte ablation; and 4) that perturbing intracellular calcium levels inhibits the ability of Langerhans cells to engulf laser-damaged keratinocytes.

Overall, our work reveals the calcium dynamics of a population of TRMs in their native microenvironment, and highlights the potential of zebrafish skin as a model for visualizing calcium activity in immune cells. Congratulations to all the authors!