Related Experiment Videos
TREM2 modulates microglia phenotypes in the neuroinflammation of Parkinson's disease
Youwen Zhang1, Shujun Feng2, Kun Nie2
1Department of Neurology, Guangdong Neuroscience Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China; Department of Neurology, The People's Hospital of Gaozhou, Guangdong, China.
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.
Insights
Triggering receptor expressed on myeloid cells-2 (TREM2) promotes protective M2 microglia polarization, reducing inflammation in Parkinson's disease (PD) models. This suggests TREM2 as a therapeutic target for PD neuroinflammation.
Area of Science:
- Neuroimmunology
- Neurodegenerative Diseases
Background:
- Neuroinflammation driven by overactivated microglia is central to Parkinson's disease (PD) pathogenesis.
- Microglia exhibit M1 (inflammatory) and M2 (immunosuppressive) phenotypes, with M1 polarization exacerbating PD.
- The mechanisms regulating microglia polarization in PD remain unclear.
Purpose of the Study:
- To investigate the role of Triggering Receptor expressed on myeloid cells-2 (TREM2) in modulating microglia polarization.
- To determine if TREM2 influences the switch from M1 to M2 microglia phenotypes.
- To assess the therapeutic potential of TREM2 in PD neuroinflammation.
Main Methods:
- Utilized a lentiviral strategy to overexpress and suppress TREM2 in BV2 microglia.
- Analyzed microglia polarization markers (M1 and M2 phenotypes) following TREM2 manipulation.
- Examined TREM2 levels and associated markers in the midbrain of PD mouse models.
Main Results:
- TREM2 was essential for M2 microglia polarization.
- TREM2 knockdown inhibited M2 polarization and exacerbated M1 inflammatory responses.
- TREM2 overexpression promoted M2 polarization and alleviated microglial inflammation.
- Elevated TREM2 levels correlated with M2 markers (Arginase-1) in PD mouse models.
Conclusions:
- TREM2 plays a critical role in shifting microglia from a pro-inflammatory M1 phenotype to a protective M2 phenotype.
- TREM2 exhibits beneficial effects in mitigating neuroinflammation associated with Parkinson's disease.
- Targeting TREM2 represents a promising therapeutic strategy for PD immune pathogenesis.