The nuclear receptor Nr4a1 mediates anti-inflammatory effects of apoptotic cells

Ipseiz N, Uderhardt S, Scholtysek C, Steffen M, Schabbauer G, Bozec A, Schett G, Krönke G (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Publisher: American Association of Immunologists

Book Volume: 192

Pages Range: 4852-8

Journal Issue: 10

DOI: 10.4049/jimmunol.1303377

Abstract

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."

Authors with CRIS profile

Involved external institutions

Medizinische Universität Wien Austria (AT)

How to cite

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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