Tissue LyC6- macrophages are generated in the absence of circulating LyC6- monocytes and Nur77 in a model of muscle regeneration

J Immunol. 2013 Dec 1;191(11):5695-701. doi: 10.4049/jimmunol.1301445. Epub 2013 Oct 16.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Ly / metabolism
  • Biomarkers / metabolism
  • Blood Circulation
  • Cardiotoxins / administration & dosage
  • Cell Differentiation* / genetics
  • Cells, Cultured
  • Humans
  • Macrophages / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Animal
  • Monocytes / immunology*
  • Muscle, Skeletal / injuries
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiology*
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / genetics
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / metabolism*
  • Regeneration / drug effects
  • Regeneration / immunology


  • Antigens, Ly
  • Biomarkers
  • Cardiotoxins
  • Ly-6C antigen, mouse
  • Nr4a1 protein, mouse
  • Nuclear Receptor Subfamily 4, Group A, Member 1