Genetic variants drive altered epigenetic regulation of endotoxin response in BTBR macrophages.

ABSTRACT: The BTBR T⁺Itpr3^tf/J (BTBR) mouse has been used as a complex genetic model of Autism Spectrum Disorders (ASD). While the specific mechanisms underlying BTBR behavioral phenotypes are poorly understood, prior studies have implicated profound differences in innate immune system control of pro-inflammatory cytokines. Innate immune activation and elevated pro-inflammatory cytokines are also detected in blood of children with ASD. In this study, we examined how underlying BTBR genetic variants correspond to strain-specific changes in chromatin accessibility, resulting in a pro-inflammatory response specifically in BTBR bone marrow derived macrophages (BMDM). In response to repeated lipopolysaccharide (LPS) treatments, C57BL/6J (C57) BMDM exhibited intact endotoxin toleranc

SUBMITTER: Ciernia AV 

PROVIDER: S-EPMC7572655 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature