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PLoS One. 2015 Jun 26;10(6):e0131702. doi: 10.1371/journal.pone.0131702. eCollection 2015.

AIM2 Drives Joint Inflammation in a Self-DNA Triggered Model of Chronic Polyarthritis.

Author information

1
Institute of Molecular Medicine, University Hospital Bonn, University of Bonn, Bonn, Germany.
2
Department of Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology Köln/Bonn, University Hospital Bonn, Bonn, Germany.

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.

PMID:
26114879
PMCID:
PMC4482750
DOI:
10.1371/journal.pone.0131702
[Indexed for MEDLINE]
Free PMC Article

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