Selective blockade of the lyso-PS lipase ABHD12 stimulates immune responses in vivo.

ABSTRACT: ABHD12 metabolizes bioactive lysophospholipids, including lysophosphatidylserine (lyso-PS). Deleterious mutations in human ABHD12 cause the neurological disease PHARC, and ABHD12^-/- mice display PHARC-like phenotypes, including hearing loss, along with elevated brain lyso-PS and features of stimulated innate immune cell function. Here, we develop a selective and in vivo-active inhibitor of ABHD12 termed DO264 and show that this compound elevates lyso-PS in mouse brain and primary human macrophages. Unlike ABHD12^-/- mice, adult mice treated with DO264 exhibited minimal perturbations in auditory function. On the other hand, both DO264-treated and ABHD12^-/- mice displayed heightened immunological responses to lymphocytic choriomeningitis virus (LCMV) clone 13

SUBMITTER: Ogasawara D 

PROVIDER: S-EPMC6263940 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature