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Biomolecules 2015, 5(3), 1302-1318;

Molecular Interactions between NR4A Orphan Nuclear Receptors and NF-κB Are Required for Appropriate Inflammatory Responses and Immune Cell Homeostasis

UCD Veterinary Sciences Centre, Conway Insitute for Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland
Author to whom correspondence should be addressed.
Academic Editor: Ivana Vancurova
Received: 30 April 2015 / Revised: 16 June 2015 / Accepted: 16 June 2015 / Published: 29 June 2015
(This article belongs to the Special Issue Transcriptional Regulation of Pro-Inflammatory Genes)
PDF [271 KB, uploaded 29 June 2015]


Appropriate innate and adaptive immune responses are essential for protection and resolution against chemical, physical or biological insults. Immune cell polarization is fundamental in orchestrating distinct phases of inflammation, specifically acute phase responses followed by resolution and tissue repair. Dysregulation of immune cell and inflammatory responses is a hallmark of multiple diseases encompassing atherosclerosis, rheumatoid arthritis, psoriasis and metabolic syndromes. A master transcriptional mediator of diverse inflammatory signaling and immune cell function is NF-κB, and altered control of this key regulator can lead to an effective switch from acute to chronic inflammatory responses. Members of the nuclear receptor (NR) superfamily of ligand-dependent transcription factors crosstalk with NF-κB to regulate immune cell function(s). Within the NR superfamily the NR4A1-3 orphan receptors have emerged as important regulators of immune cell polarization and NF-κB signaling. NR4A receptors modulate NF-κB activity in a dynamic fashion, either repressing or enhancing target gene expression leading to altered inflammatory outcome. Here we will discuss the pivotal role NR4A’s receptors play in orchestrating immune cell homeostasis through molecular crosstalk with NF-κB. Specifically, we will examine such NR4A/NF-κB interactions within the context of distinct cell phenotypes, including monocyte, macrophage, T cells, endothelial, and mesenchymal cells, which play a role in inflammation-associated disease. Finally, we review the therapeutic potential of altering NR4A/NF-κB interactions to limit hyper-inflammatory responses in vivo. View Full-Text
Keywords: nuclear receptors; NR4A subfamily; NF-κB; inflammation; immune homeostasis nuclear receptors; NR4A subfamily; NF-κB; inflammation; immune homeostasis

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Murphy, E.P.; Crean, D. Molecular Interactions between NR4A Orphan Nuclear Receptors and NF-κB Are Required for Appropriate Inflammatory Responses and Immune Cell Homeostasis. Biomolecules 2015, 5, 1302-1318.

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