Ipseiz N, Uderhardt S, Scholtysek C, Steffen M, Schabbauer G, Bozec A, Schett G, Krönke G (2014)
Publication Type: Journal article
Publication year: 2014
Publisher: American Association of Immunologists
Book Volume: 192
Pages Range: 4852-8
Journal Issue: 10
Uptake of apoptotic cells (ACs) by macrophages ensures the nonimmunogenic clearance of dying cells, as well as the maintenance of self-tolerance to AC-derived autoantigens. Upon ingestion, ACs exert an inhibitory influence on the inflammatory signaling within the phagocyte. However, the molecular signals that mediate these immune-modulatory properties of ACs are incompletely understood. In this article, we show that the phagocytosis of apoptotic thymocytes was enhanced in tissue-resident macrophages where this process resulted in the inhibition of NF-?B signaling and repression of inflammatory cytokines, such as IL-12. In parallel, ACs induced a robust expression of a panel of immediate early genes, which included the Nr4a subfamily of nuclear receptors. Notably, deletion of Nr4a1 interfered with the anti-inflammatory effects of ACs in macrophages and restored both NF-?B signaling and IL-12 expression. Accordingly, Nr4a1 mediated the anti-inflammatory properties of ACs in vivo and was required for maintenance of self-tolerance in the murine model of pristane-induced lupus. Thus, our data point toward a key role for Nr4a1 as regulator of the immune response to ACs and of the maintenance of tolerance to "dying self."
APA:
Ipseiz, N., Uderhardt, S., Scholtysek, C., Steffen, M., Schabbauer, G., Bozec, A.,... Krönke, G. (2014). The nuclear receptor Nr4a1 mediates anti-inflammatory effects of apoptotic cells. Journal of Immunology, 192(10), 4852-8. https://doi.org/10.4049/jimmunol.1303377
MLA:
Ipseiz, Natacha, et al. "The nuclear receptor Nr4a1 mediates anti-inflammatory effects of apoptotic cells." Journal of Immunology 192.10 (2014): 4852-8.
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