Cellular uptake of extracellular nucleosomes induces innate immune responses by binding and activating cGMP-AMP synthase (cGAS).

ABSTRACT: The nucleosome is the basic structural repeating unit of chromatin. DNA damage and cell apoptosis release nucleosomes into the blood circulatory system, and increased levels of circulating nucleosomes have been observed to be related to inflammation and autoimmune diseases. However, how circulating nucleosomes trigger immune responses has not been fully elucidated. cGAS (cGMP-AMP synthase) is a recently discovered pattern recognition receptor that senses cytoplasmic double-stranded DNA (dsDNA). In this study, we employed in vitro reconstituted nucleosomes to examine whether extracellular nucleosomes can gain access to the cytoplasm of mammalian cells to induce immune responses by activating cGAS. We showed that nucleosomes can be taken up by various mammalian cells. Additionally, we found

SUBMITTER: Wang H 

PROVIDER: S-EPMC7505961 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature