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: | Varga T, Mounier R, Gogolak P, Poliska S, Chazaud B, Nagy L |
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Journal: | J. Immunol.; 2013 Dec 01; 191(11) 5695-701. doi:10.4049/jimmunol.1301445 |
Year: | 2013 |
PubMed: | PMID: 24133167 (Go to PubMed) |