title: Tissue LyC6- macrophages are generated in the absence of circulating LyC6- monocytes and Nur77 in a model of muscle regeneration.
abstract: There are several open questions regarding the origin, development, and differentiation of subpopulations of monocytes, macrophages (MFs), and dendritic cells. It is a particularly intriguing question how circulating monocyte subsets develop and contribute to the generation of steady-state and inflammatory tissue MF pools and which transcriptional mechanisms contribute to these processes. In this study, we took advantage of a genetic model in which LyC6(-) circulating monocyte development is severely diminished due to the lack of the nuclear receptor, NUR77. We show that, in a mouse model of skeletal muscle injury and regeneration, the accumulation of leukocytes and the generation of LyC6(+) and LyC6(-) MF pools are intact in the absence of circulating LyC6(-) blood monocytes. These data suggest that NUR77, which is required for LyC6(-) blood monocyte development, is expressed but not critically required for LyC6(+) to LyC6(-) tissue MF specification. Moreover, these observations support a model according to which tissue macrophage subtype specification is distinct from that of circulating monocytes. Lastly, our data show that in the used sterile inflammation model tissue LyC6(-) MFs are derived from LyC6(+) cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Research Center for Molecular Medicine, Medical and Health Science Center, University of Debrecen, Debrecen 4012, Hungary;
authors.forename: Tamas
authors.initials: T
authors.lastname: Varga
authors.forename: Rémi
authors.initials: R
authors.lastname: Mounier
authors.forename: Peter
authors.initials: P
authors.lastname: Gogolak
authors.forename: Szilard
authors.initials: S
authors.lastname: Poliska
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Chazaud
authors.forename: Laszlo
authors.initials: L
authors.lastname: Nagy
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001775:Blood Circulation; D054715:Cardiotoxins / Q000008:administration & dosage; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D009000:Monocytes / Q000276:immunology*; D018482:Muscle, Skeletal / Q000293:injuries / Q000473:pathology / Q000502:physiology*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000235:genetics / Q000378:metabolism*; D012038:Regeneration / Q000187:drug effects / Q000276:immunology
chemical_list: D000950:Antigens, Ly; D015415:Biomarkers; D054715:Cardiotoxins; C494192:Ly-6C antigen, mouse; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1