CXCR4 marks homeostatically activated dendritic cells in the steady-state and in cancer
Conventional dendritic cells (cDCs) drive T cell immunity to infection but can also promote tolerance at steady state through “homeostatic activation”. However, homeostatically activated cDCs closely resemble those activated by microbial or viral stimuli, hindering their study. Here, we identify the chemokine receptor CXCR4 as a specific marker of these cells across mouse tissues. CXCR4 is induced in cDCs in the steady state but not following stimulation with Toll-like receptor agonists or type I interferons. In tumours, CXCR4 expression or a gene signature derived from mouse spleen CXCR4hi cDCs marks so-called “mregDCs” that have acquired tumor-derived material and mirror homeostatically activated cells. Notably, this gene signature further identifies “mregDCs” in human cancers. Thus, CXCR4 distinguishes homeostatic from inflammatory cDC activation programs, providing a means to identify and study a putatively tolerogenic cDC state that is also co-opted in cancer.