Barreiro, OlgaCibrian, DanayClemente, CristinaAlvarez, DavidMoreno, VanessaValiente, ÍñigoBernad, AntonioVestweber, DietmarArroyo, Alicia GMartín, Pilarvon Andrian-Werburg, UlrichSánchez Madrid, Francisco2016-08-092016Barreiro, O., D. Cibrian, C. Clemente, D. Alvarez, V. Moreno, Í. Valiente, A. Bernad, et al. 2016. “Pivotal role for skin transendothelial radio-resistant anti-inflammatory macrophages in tissue repair.” eLife 5 (1): e15251. doi:10.7554/eLife.15251. http://dx.doi.org/10.7554/eLife.15251.2050-084Xhttp://nrs.harvard.edu/urn-3:HUL.InstRepos:27822237Heterogeneity and functional specialization among skin-resident macrophages are incompletely understood. In this study, we describe a novel subset of murine dermal perivascular macrophages that extend protrusions across the endothelial junctions in steady-state and capture blood-borne macromolecules. Unlike other skin-resident macrophages that are reconstituted by bone marrow-derived progenitors after a genotoxic insult, these cells are replenished by an extramedullary radio-resistant and UV-sensitive Bmi1+ progenitor. Furthermore, they possess a distinctive anti-inflammatory transcriptional profile, which cannot be polarized under inflammatory conditions, and are involved in repair and remodeling functions for which other skin-resident macrophages appear dispensable. Based on all their properties, we define these macrophages as Skin Transendothelial Radio-resistant Anti-inflammatory Macrophages (STREAM) and postulate that their preservation is important for skin homeostasis. DOI: http://dx.doi.org/10.7554/eLife.15251.001en-USintravital imagingmacrophageswound healingMouseJournal Article2016-08-0910.7554/eLife.15251