1,25-Dihydroxy Vitamin D3 Facilitates the M2 Polarization and β-Amyloid Uptake by Human Microglia in a TREM2-Dependent Manner

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by dementia as the primary clinical symptom. The production and accumulation of aggregated beta-amyloid (A beta) in patient brain tissues is one of the hallmarks of AD pathogenesis. Microglia, brain-resident macrophages, produce inflammatory cytokines in response to A beta oligomers or fibrils exacerbating A beta pathology in AD. HMO6 cells were treated with A beta 42 in the presence or absence of 1,25-dihydroxy vitamin D-3 (1,25(OH)(2)D-3) to determine its potential immunomodulatory effects, and the expression of pro-/anti-inflammatory cytokines, M1/M2-associated markers, Toll-like receptors (TLRs), and triggering receptor expressed on myeloid cells 2 (TREM2) was examined. 1,25(OH)(2)D-3 was found to suppress A beta-induced expression of proinflammatory cytokines (TNF-alpha, IL-1 beta, and IL-6), M1 markers (CD86 and iNOS), and TLR2/4, whilst increasing the expression of anti-inflammatory cytokines (IL-4, IL-10, and CCL17) and M2 markers (CD206 and Arg-1). Furthermore, 1,25(OH)(2)D-3 promoted TREM2 expression and A beta uptake by HMO6 cells, and the enhancement of A beta uptake and M2 polarization was revealed to be TREM2-dependent. The findings of this study suggest that 1,25(OH)(2)D-3 facilitates M2 polarization and A beta uptake in a TREM2-dependent manner.