TY - JOUR
T1 - Tissue LyC6- macrophages are generated in the absence of circulating LyC6- monocytes and Nur77 in a model of muscle regeneration
AU - Varga, Tamas
AU - Mounier, Rémi
AU - Gogolak, Peter
AU - Poliska, Szilard
AU - Chazaud, Bénédicte
AU - Nagy, Laszlo
PY - 2013/12/1
Y1 - 2013/12/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1301445
DO - 10.4049/jimmunol.1301445
M3 - Article
C2 - 24133167
AN - SCOPUS:84888370511
SN - 0022-1767
VL - 191
SP - 5695
EP - 5701
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -