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: Christopher Jakobs, Sven Perner, Veit Hornung
• Journal: PloS one (PLoS One) Vol. 10 Issue 6 Pg. e0131702 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26114879 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aim2 protein, mouse
• Autoantigens
• DNA-Binding Proteins
• Ifnar1 protein, mouse
• Inflammasomes
• Receptor, Interferon alpha-beta
• DNA
• Endodeoxyribonucleases
• deoxyribonuclease II

Topics

• Animals
• Arthritis, Experimental (genetics, pathology)
• Autoantigens (metabolism)
• DNA (adverse effects, metabolism)
• DNA-Binding Proteins (genetics, physiology)
• Disease Models, Animal
• Endodeoxyribonucleases (genetics)
• Inflammasomes (genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Receptor, Interferon alpha-beta (genetics)