LILRB2-mediated TREM2 signaling inhibition suppresses microglia functions.

ABSTRACT:

Background

Microglia plays crucial roles in Alzheimer's disease (AD) development. Triggering receptor expressed on myeloid cells 2 (TREM2) in association with DAP12 mediates signaling affecting microglia function. Here we study the negative regulation of TREM2 functions by leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2), an inhibitory receptor bearing ITIM motifs.

Methods

To specifically interrogate LILRB2-ligand (oAβ and PS) interactions and microglia functions, we generated potent antagonistic LILRB2 antibodies with sub-nanomolar level activities. The biological effects of LILRB2 antagonist antibody (Ab29) were studied in human induced pluripotent stem cell (iPSC)-derived microglia (hMGLs) for migration, oAβ phagocytosis, and upregulation of inflammato

SUBMITTER: Zhao P 

PROVIDER: S-EPMC9206387 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature