1,25-Dihydroxy Vitamin D 3 Facilitates the M2 Polarization and β -Amyloid Uptake by Human Microglia in a TREM2-Dependent Manner.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by dementia as the primary clinical symptom. The production and accumulation of aggregated β -amyloid (A β ) in patient brain tissues is one of the hallmarks of AD pathogenesis. Microglia, brain-resident macrophages, produce inflammatory cytokines in response to A β oligomers or fibrils exacerbating A β pathology in AD. HMO6 cells were treated with A β 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 β -induced expression of proinflammatory cytokines (TNF- α , IL-1 β , 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 β uptake by HMO6 cells, and the enhancement of A β 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 β uptake in a TREM2-dependent manner.