title: AIM2 Drives Joint Inflammation in a Self-DNA Triggered Model of Chronic Polyarthritis.
abstract: Mice lacking DNase II display a polyarthritis-like disease phenotype that is driven by translocation of self-DNA into the cytoplasm of phagocytic cells, where it is sensed by pattern recognition receptors. While pro-inflammatory gene expression is non-redundantly linked to the presence of STING in these mice, the contribution of the inflammasome pathway has not been explored. To this end, we studied the role of the DNA-sensing inflammasome receptor AIM2 in this self-DNA driven disease model. Arthritis-prone mice lacking AIM2 displayed strongly decreased signs of joint inflammation and associated histopathological findings. This was paralleled with a reduction of caspase-1 activation and pro-inflammatory cytokine production in diseased joints. Interestingly, systemic signs of inflammation that are associated with the lack of DNase II were not dependent on AIM2. Taken together, these data suggest a tissue-specific role for the AIM2 inflammasome as a sensor for endogenous DNA species in the course of a ligand-dependent autoinflammatory condition.
authors.affiliation: Institute of Molecular Medicine, University Hospital Bonn, University of Bonn, Bonn, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Jakobs
authors.affiliation: Department of Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology Köln/Bonn, University Hospital Bonn, Bonn, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
authors.affiliation: Institute of Molecular Medicine, University Hospital Bonn, University of Bonn, Bonn, Germany.
authors.forename: Veit
authors.initials: V
authors.lastname: Hornung
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics* / Q000473:pathology; D001324:Autoantigens / Q000378:metabolism; D004247:DNA / Q000009:adverse effects / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D004706:Endodeoxyribonucleases / Q000235:genetics*; D058847:Inflammasomes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053633:Receptor, Interferon alpha-beta / Q000235:genetics
chemical_list: C540422:Aim2 protein, mouse; D001324:Autoantigens; D004268:DNA-Binding Proteins; C508032:Ifnar1 protein, mouse; D058847:Inflammasomes; D053633:Receptor, Interferon alpha-beta; D004247:DNA; D004706:Endodeoxyribonucleases; C019329:deoxyribonuclease II