Pivotal role for skin transendothelial radio-resistant anti-inflammatory macrophages in tissue repair.
Heterogeneity 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.
Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
Olga
O
Barreiro
Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.|Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Madrid, Spain.|Instituto Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Madrid, Spain.
Danay
D
Cibrian
Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
Cristina
C
Clemente
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, United States.
David
D
Alvarez
Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
Vanessa
V
Moreno
Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
Íñigo
Í
Valiente
Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
Antonio
A
Bernad
Max Planck Institute of Molecular Biomedicine, Münster, Germany.
Dietmar
D
Vestweber
Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
Alicia G
AG
Arroyo
Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
Pilar
0000-0002-2392-1764
P
Martín
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, United States.|Ragon Institute of MGH, MIT and Harvard, Cambridge, United States.
Ulrich H
UH
von Andrian
Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.|Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Madrid, Spain.|Instituto Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Madrid, Spain.
Francisco
0000-0001-5303-0762
F
Sánchez Madrid
D000818:Animals; D006706:Homeostasis; D008264:Macrophages / Q000145:classification* / Q000502:physiology*; D051379:Mice; D012867:Skin / Q000166:cytology* / Q000276:immunology*
immunology; intravital imaging; macrophages; mouse; wound healing