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Immunity. 2015 Jul 21;43(1):92-106. doi: 10.1016/j.immuni.2015.06.012. Epub 2015 Jul 7.

Genetic Cell Ablation Reveals Clusters of Local Self-Renewing Microglia in the Mammalian Central Nervous System.

Author information

1
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Obere Zahlbacher Str. 67, 55131 Mainz, Germany.
2
Institute for Medical Biometry, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg-University Mainz, Obere Zahlbacher Str. 69, 55131 Mainz, Germany.
3
Department of Neurology, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstr.1, 55131 Mainz, Germany.
4
Institute for Immunology, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstr.1, 55131 Mainz, Germany.
5
Department of Neuropathology & BIOSS Centre for Biological Signaling Studies, University of Freiburg, Breisacher Str. 64, 79098 Freiburg, Germany.
6
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
7
Department for Internal Medicine, University Hospital, 93042 Regensburg, Germany.
8
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
9
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Obere Zahlbacher Str. 67, 55131 Mainz, Germany. Electronic address: waisman@uni-mainz.de.

Abstract

During early embryogenesis, microglia arise from yolk sac progenitors that populate the developing central nervous system (CNS), but how the tissue-resident macrophages are maintained throughout the organism's lifespan still remains unclear. Here, we describe a system that allows specific, conditional ablation of microglia in adult mice. We found that the microglial compartment was reconstituted within 1 week of depletion. Microglia repopulation relied on CNS-resident cells, independent from bone-marrow-derived precursors. During repopulation, microglia formed clusters of highly proliferative cells that migrated apart once steady state was achieved. Proliferating microglia expressed high amounts of the interleukin-1 receptor (IL-1R), and treatment with an IL-1R antagonist during the repopulation phase impaired microglia proliferation. Hence, microglia have the potential for efficient self-renewal without the contribution of peripheral myeloid cells, and IL-1R signaling participates in this restorative proliferation process.

PMID:
26163371
DOI:
10.1016/j.immuni.2015.06.012
[Indexed for MEDLINE]
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