Guerrero Pearl A Leon, Rasmussen Jeffrey P, Peterman Eric
Department of Biology, University of Washington, Seattle, WA.
Institute for Stem Cells and Regenerative Medicine, University of Washington, Seattle WA.
bioRxiv. 2024 Sep 26:2024.09.24.614510. doi: 10.1101/2024.09.24.614510.
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.
免疫细胞依赖于细胞内钙活性的快速变化来调节细胞功能。皮肤包含多种免疫细胞类型，并且在很大程度上依赖钙信号来维持稳态和进行修复，然而皮肤免疫细胞中钙的动态变化和功能仍知之甚少。在这里，我们描述了朗格汉斯细胞中的钙活性，朗格汉斯细胞是驻留在皮肤中的巨噬细胞，负责在组织损伤后监测和清除细胞碎片。朗格汉斯细胞位于表皮中，并在紧邻相邻角质形成细胞和躯体感觉外周轴突的位置延伸出动态树突。我们发现，稳态下的朗格汉斯细胞表现出钙活性的自发和短暂变化，钙通量主要发生在细胞体中，很少发生在树突中。触发躯体感觉轴突退化会增加朗格汉斯细胞树突中钙活性的频率。相比之下，我们发现朗格汉斯细胞在吞噬受损角质形成细胞后，细胞内钙会持续增加。改变细胞内钙活性会导致角质形成细胞碎片的吞噬效率降低。我们的研究结果表明，朗格汉斯细胞表现出钙活性的上下文特异性变化，并突出了皮肤作为组织驻留巨噬细胞钙动力学成像的可及模型的实用性。
