Nr4a1-dependent Ly6Clow monocytes monitor endothelial cells and orchestrate their disposal

Leo M. Carlin, Efstathios G. Stamatiades, Cedric Auffray, Richard N. Hanna, Leanne Glover, Gema Vizcay-Barrena, Catherine C. Hedrick, H. Terence Cook, Sandra Diebold, Frederic Geissmann

Research output: Contribution to journalArticlepeer-review

518 Scopus citations


The functions of Nr4a1-dependent Ly6Clow monocytes remain enigmatic. We show that they are enriched within capillaries and scavenge microparticles from their lumenal side in a steady state. In the kidney cortex, perturbation of homeostasis by a TLR7-dependent nucleic acid "danger" signal, which may signify viral infection or local cell death, triggers Gαi-dependent intravascular retention of Ly6Clow monocytes by the endothelium. Then, monocytes recruit neutrophils in a TLR7-dependent manner to mediate focal necrosis of endothelial cells, whereas the monocytes remove cellular debris. Prevention of Ly6Clow monocyte development, crawling, or retention in Nr4a1-/-, Itgal-/-, and Tlr7host-/-BM+/+ and Cx3cr1-/- mice, respectively, abolished neutrophil recruitment and endothelial killing. Prevention of neutrophil recruitment in Tlr7host+/+BM-/- mice or by neutrophil depletion also abolished endothelial cell necrosis. Therefore, Ly6C low monocytes are intravascular housekeepers that orchestrate the necrosis by neutrophils of endothelial cells that signal a local threat sensed via TLR7 followed by the in situ phagocytosis of cellular debris.

Original languageEnglish (US)
Pages (from-to)362-375
Number of pages14
Issue number2
StatePublished - Apr 11 2013
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


Dive into the research topics of 'Nr4a1-dependent Ly6Clow monocytes monitor endothelial cells and orchestrate their disposal'. Together they form a unique fingerprint.

Cite this