Immunity
Volume 38, Issue 1, 24 January 2013, Pages 79-91
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Article
Fate Mapping Reveals Origins and Dynamics of Monocytes and Tissue Macrophages under Homeostasis

https://doi.org/10.1016/j.immuni.2012.12.001Get rights and content
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Summary

Mononuclear phagocytes, including monocytes, macrophages, and dendritic cells, contribute to tissue integrity as well as to innate and adaptive immune defense. Emerging evidence for labor division indicates that manipulation of these cells could bear therapeutic potential. However, specific ontogenies of individual populations and the overall functional organization of this cellular network are not well defined. Here we report a fate-mapping study of the murine monocyte and macrophage compartment taking advantage of constitutive and conditional CX3CR1 promoter-driven Cre recombinase expression. We have demonstrated that major tissue-resident macrophage populations, including liver Kupffer cells and lung alveolar, splenic, and peritoneal macrophages, are established prior to birth and maintain themselves subsequently during adulthood independent of replenishment by blood monocytes. Furthermore, we have established that short-lived Ly6C+ monocytes constitute obligatory steady-state precursors of blood-resident Ly6C cells and that the abundance of Ly6C+ blood monocytes dynamically controls the circulation lifespan of their progeny.

Highlights

► Most tissue macrophages are established before birth and are self-maintaining ► Ly6C+ monocytes are obligatory precursors of Ly6C monocytes in steady state ► Ly6C+ monocytes negatively control lifespan of Ly6C monocytes as Csf-1 sink

Cited by (0)

6

These authors contributed equally to this work

7

Present address: Division of Medicine, University College London, London WC1 6JJ, UK

8

Present address: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA

9

Present address: Laboratory of Immunoregulation and Mucosal Immunology, Department for Molecular Biomedical Research, VIB, Ghent, Belgium