ACKR3 in Skin Homeostasis, an Overlooked Player in the CXCR4/CXCL12 Axis

CXCL12 and its receptor CXCR4 emerge as critical regulators within the intricate network of processes ensuring skin homeostasis. In this review, we discuss their spatial distribution and function in steady-state skin; delve into their role in acute wound healing, with emphasis on fibrotic and regenerative responses; and explore their relevance in skin responses to commensals and pathogens. Given the lack of knowledge surrounding ACKR3, the atypical receptor of CXCL12, we speculate whether and how it might be involved in the processes mentioned earlier. Is ACKR3 the (a)typical friend who enjoys missing the party, or do we need to take a closer look?