Retinoid-related orphan receptors (RORs): critical roles in development, immunity, circadian rhythm, and cellular metabolism

By A. Jetten. Nuclear Receptor Signaling, 2009

664 citations recorded by the source corpus.

The last few years have witnessed a rapid increase in our knowledge of the retinoid-related orphan receptors RORα, -β, and -γ (NR1F1-3), their mechanism of action, physiological functions, and their potential role in several pathologies. The characterization of ROR-deficient mice and gene expression profiling in particular have provided great insights into the critical functions of RORs in the regulation of a variety of physiological processes. These studies revealed that RORa plays a critical role in the development of the cerebellum, that both RORα and RORβ are required for the maturation of photoreceptors in the retina, and that RORγ is essential for the development of several secondary lymphoid tissues, including lymph nodes. RORs have been further implicated in the regulation of various metabolic pathways, energy homeostasis, and thymopoiesis. Recent studies identified a critical role for RORγ in lineage specification of uncommitted CD4+T helper cells into Th17 cells. In addition, RORs regulate the expression of several components of the circadian clock and may play a role in integrating the circadian clock and the rhythmic pattern of expression of downstream (metabolic) genes. Study of ROR target genes has provided insights into the mechanisms by which RORs control these processes. Moreover, several reports have presented evidence for a potential role of RORs in several pathologies, including osteoporosis, several autoimmune diseases, asthma, cancer, and obesity, and raised the possibility that RORs may serve as potential targets for chemotherapeutic intervention. This prospect was strengthened by recent evidence showing that RORs can function as ligand-dependent transcription factors.

Subfields: Biochemistry, Endocrine and Autonomic Systems, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9bba7d535f0d6ce3cd8f63c4281d197c552a0508

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In Biochemistry

1. W. Fung-Leung
2. Xuejun Liu
3. A. Bittner
4. Shanrong Zhao
5. K. Ngo

In Endocrine and Autonomic Systems

1. W. Fung-Leung
2. Xuejun Liu
3. A. Bittner
4. Shanrong Zhao
5. K. Ngo

In Molecular Biology

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2. D. Mathis
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4. A. Bittner
5. Shanrong Zhao
6. K. Ngo
7. C. Benoist

Citations in the corpus

• Melatonin membrane receptors in peripheral tissues: Distribution and functions (2012, neutral): “However, some investigators question the ability of melatonin to bind to the nuclear receptor RORα and to directly activate it (Dai et al., 2001).”
• Comparison of RNA-Seq and Microarray in Transcriptome Profiling of Activated T Cells (2014, methodology): “RORct is an orphan nuclear receptor playing an important regulatory role in promoting differentiation of CD4 T cells into pro-inflammatory T helper 17 (Th17) cells [26].”
• Individual intestinal symbionts induce a distinct population of RORγ+ regulatory T cells (2015, background): “The context-specificity of Rorγ's transcriptional footprint is in line with its broad involvement in many immunological and non-immunological processes (organogenesis, circadian rhythm, lipid metabolism) (15, 30).”