Extracellular Caspase-1 regulates migration of hair follicle stem cells upon wounding

Migration of stem cells from one niche to another is a fundamental behavior observed during developmental processes such as organ specification and in homeostasis such as tissue regeneration and wound healing. A common theme running throughout these phenomena is the ability of cells to communicate with their environment to direct these stem cells to a specific location at a specific time. Deregulation of such cellular responses can lead to conditions such as developmental defects, tumor metastasis and ineffective wound closure. Wound healing is a physiological process that is activated upon tissue damage, which involves activation and migration of various cell types leading to the repair of the wounded tissue. In the context of the skin, wounding activates various resident stem cell pools including multipotent hair follicle stem cells, but how these cells are mobilized and directed to the damaged area has been an intractable problem for almost two decades. Wounded keratinocytes activate and secrete Caspase-1, a cytosolic protein well known as a critical regulator of inflammation. Surprisingly, we find that extracellular caspase-1 has a non-catalytic role of activating chemotaxis of hair follicle stem cells into the wound bed. This exemplifies a novel function of an inflammatory molecule in recruiting adult stem cells that may underlie the epithelial hyperplasia found to accompany many inflammatory diseases.