Tissue LyC6? Macrophages Are Generated in the Absence of Circulating LyC6? Monocytes and Nur77 in a Model of Muscle Regeneration

摘要

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.