1. Microglia control small vessel calcification via TREM2
- Author
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Mauro Delorenzi, Melanie Greter, Sina Nassiri, Marco Colonna, Elisabeth J. Rushing, Yvette Zarb, Upasana Maheshwari, Annika Keller, Sebastian G. Utz, Johanna Schaffenrath, Sucheta Sridhar, K. Peter R. Nilsson, University of Zurich, and Keller, Annika
- Subjects
Pathology ,medicine.medical_specialty ,Cell- och molekylärbiologi ,Central nervous system ,10208 Institute of Neuropathology ,610 Medicine & health ,10180 Clinic for Neurosurgery ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Pathological ,Research Articles ,030304 developmental biology ,1000 Multidisciplinary ,0303 health sciences ,Multidisciplinary ,Microglia ,business.industry ,TREM2 ,SciAdv r-articles ,medicine.disease ,Phenotype ,medicine.anatomical_structure ,nervous system ,Small vessel ,Adult ,Diet ,Diving ,Humans ,Male ,Military Personnel ,Naval Medicine ,Nutritional Status ,United States ,business ,Cell and Molecular Biology ,030217 neurology & neurosurgery ,Homeostasis ,Research Article ,Neuroscience ,Calcification - Abstract
Microglia participate in central nervous system (CNS) development and homeostasis and are often implicated in modulating disease processes. However, less is known about the role of microglia in the biology of the neurovascular unit (NVU). In particular, data are scant on whether microglia are involved in CNS vascular pathology. In this study, we use a mouse model of primary familial brain calcification, Pdgfbret/ret, to investigate the role of microglia in calcification of the NVU. We report that microglia enclosing vessel calcifications, coined calcification-associated microglia, display a distinct activation phenotype. Pharmacological ablation of microglia with the CSF1R inhibitor PLX5622 leads to aggravated vessel calcification. Mechanistically, we show that microglia require functional TREM2 for controlling vascular calcification. Our results demonstrate that microglial activity in the setting of pathological vascular calcification is beneficial. In addition, we identify a previously unrecognized function of microglia in halting the expansion of vascular calcification., Science Advances, 7 (9), ISSN:2375-2548
- Published
- 2021
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