sTREM2 and ApoE Isoforms Differentially Regulate Cytokine Expression in Myeloid-Derived Cell Models.

Abstract

TREM2 is an innate immune receptor expressed in microglia and macrophages. ApoE isoforms (E2/E3/E4) are ligands of TREM2. TREM2 variants and ApoE4 are top risk factors of Alzheimer’s disease. TREM2 can be cleaved from cell membrane as soluble TREM2 (sTREM2), the level of which fluctuates during Alzheimer’s progression. However, the mechanisms that sTREM2 and the interactions between TREM2 and ApoE may contribute to Alzheimer’s neuroinflammation are largely uncharacterized. The project objectives were to investigate whether sTREM2 and ApoE isoforms can affect cytokine expression profiles in myeloid-derived cell models. My results show that sTREM2 can stimulate inflammatory cytokine expression at early time-point but anti-inflammatory cytokine expression at later time-point mainly via MAPK-JNK signaling pathway. sTREM2 has differential effects on cytokine expression in M0, M1, and M2 macrophages. ApoE isoforms also differentially induce cytokine expression and regulate TREM2 expression in M0, M1, and M2 macrophages. My study reveals a complex interplay of sTREM2, TREM2 and ApoE isoforms and differential effects of those in the models.