TREM2 modulates microglia phenotypes in the neuroinflammation of Parkinson's disease - PubMed (original) (raw)
. 2018 May 23;499(4):797-802.
doi: 10.1016/j.bbrc.2018.03.226. Epub 2018 Apr 4.
Affiliations
- PMID: 29621548
- DOI: 10.1016/j.bbrc.2018.03.226
TREM2 modulates microglia phenotypes in the neuroinflammation of Parkinson's disease
Youwen Zhang et al. Biochem Biophys Res Commun. 2018.
Abstract
Neuroinflammation and overactivated microglia underlies the pathogenesis of Parkinson's disease (PD). Furthermore, microglia could polarize into classic inflammatory M1 and immunosuppressive M2 phenotype. Thus, inhibiting the overactivated inflammatory M1 microglia by promoting the transformation of microglia to the protective M2 phenotype provides potential therapy for PD, but the mechanism that modulates microglia polarization remains unknown. Triggering receptor expressed on myeloid cells-2 (TREM2) is a recently identified immune receptor expressed by the microglia in the brain. Emerging evidence indicates that TREM2 enhances the phagocytosis function of microglia and suppress inflammation. Based on these evidence, we hypothesized that TREM2 might play a protective role through regulating microglia polarization. Here, we employ a lentiviral strategy to overexpress or suppress TREM2 on microglia and found that TREM2 was essential for M2 microglia polarization. Knockdown of TREM2 in BV2 microglia inhibited M2 polarization and lead to exaggeration of M1 microglial inflammatory responses, whereas overexpression of TREM2 promoted M2 polarization and alleviated microglial inflammation. We also observed that the TREM2 level was higher in the midbrain of PD mice, which was accompanied by an elevated level of Arginase-1 and increased proinflammatory cytokines, suggesting that TREM2 is an important factor in switching the microglia phenotypes. Taken together, these findings indicate that TREM2 plays a crucial role in altering the proinflammatory M1 microglia to M2 phenotype and has beneficial effects in the immune pathogenesis of PD.
Keywords: Microglia; Neuroinflammation; Parkinson's disease; Polarization; Triggering receptor expressed on myeloid cells 2.
Copyright © 2018 Elsevier Inc. All rights reserved.
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