Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose:
The nuclear receptor NR4A1 has been implicated as negative feedback regulator of NF kappa B signalling and as key regulator during the differentiation of Ly6C-low resident monocytes. Apoptotic cells are known to exert anti-inflammatory effects on macrophages but the underlying mechanisms are still poorly understood. Here we studied a potential role of NR4A1 as mediator of the macrophage response to apoptotic cells.
Methods:
We analysed the effect of apoptotic thymocytes on wild type and NR4A1-/- peritoneal resident macrophages, and determined the consequences on intracellular signalling, gene expression and cytokine profile. Moreover, we examined the consequences of the lack of NR4A1 during maintenance of self tolerance by using the pristine-induced model of murine sytemic lupus erythematosus.
Results:
Expresion of NR4A1 was rapidly and highly induced in resident macrophages after incubation with apoptotic thymocytes. NR4A1-/- resident macrophages showed an exacerbated pro-inflammatory profile as well as an increased activity of NF-κB. Moreover, the anti-inflammatory effects of apoptotic cells were reduced in NR4A1-/- macrophages. In the pristine model of murine lupus, NR4A1-/- mice displayed increased levels of autoantibodies such as ds-DNA antibodies.
Conclusion:
Our data show for the first time that NR4A1 is an important mediator of the anti-inflammatory effects of apoptotic cells in tissue resident macrophages and thereby contributes to the maintenance of self-tolerance.
Disclosure:
N. Ipseiz,
None;
S. Uderhardt,
None;
G. A. Schett,
None;
G. Kronke,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/nr4a1-mediates-anti-inflammatory-effects-of-apoptotic-cells/