title: DNA-responsive inflammasomes and their regulators in autoimmunity.
abstract: Upon sensing microbial and self-derived DNA, DNA sensors initiate innate immune responses. These sensors include the interferon (IFN)-inducible Toll-like receptor 9 (TLR9) and PYHIN proteins. Upon sensing DNA, cytosolic (murine Aim2 and human AIM2) and nuclear (IFI16) PYHIN proteins recruit an adaptor protein (ASC) and pro-caspase-1 to form an inflammasome, which activates caspase-1. The activated caspase-1 cleaves pro-IL-1β and pro-IL-18 to generate active forms. However, upon sensing cytosolic DNA, the IFI16 protein recruits STING to induce the expression of type I IFN. Recognition of self DNA by innate immune cells contributes to the production of increased levels of type I IFN. Given that the type I IFNs modulate the expression of inflammasome proteins and that the IFN-inducible proteins inhibit the activity of DNA-responsive inflammasomes, an improved understanding of the molecular mechanisms that regulate the activity of DNA-responsive inflammasomes is likely to identify new therapeutic targets to treat autoimmune diseases.
authors.affiliation: Department of Environmental Health, University of Cincinnati, 3223 Eden Avenue, P. O. Box 670056, Cincinnati, OH 45267, USA. Divaker.choubey@uc.edu
authors.forename: Divaker
authors.initials: D
authors.lastname: Choubey
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity; D004247:DNA / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000276:immunology*
chemical_list: D058847:Inflammasomes; D004247:DNA