Chromatin Dynamics and Genetic Variation Combine to Regulate Innate Immune Memory

Recent work by Ciernia et al. (2020) identified how genetic and epigenetic mechanisms interact to regulate innate immune memory in bone marrow derived macrophages. The authors examined the BTBR strain, a naturally occurring mouse model of Autism Spectrum Disorder (ASD) that captures the complex genetics, behavioral and immune dysregulation found in the human disorder. Immune cell cultures from the BTBR strain compared to the standard C57 showed hyper-responsive immune gene expression that was linked to altered chromatin accessibility at sites with genetic differences between the strains. Together, findings from this work demonstrated that multiple levels of gene regulation likely dictate the formation of innate immune memory and are likely disrupted in immune cells in ASD. Future work will be needed to extend these findings to immune gene regulation in the brain and how changes in immune function are related to abnormal behaviors in brain disorders.