Retinoid X receptor α controls innate inflammatory responses through the up-regulation of chemokine expression
Open accessAbstract
The retinoid X receptor α (RXRα) plays a central role in the regulation of many intracellular receptor signaling pathways and can mediate ligand-dependent transcription by forming homodimers or heterodimers with other nuclear receptors. Although several members of the nuclear hormone receptor superfamily have emerged as important regulators of macrophage gene expression, the existence in vivo of an RXR signaling pathway in macrophages has not been established. Here, we provide evidence that RXRα regulates the transcription of the chemokines Ccl6 and Ccl9 in macrophages independently of heterodimeric partners. Mice lacking RXRα in myeloid cells exhibit reduced levels of CCL6 and CCL9, impaired recruitment of leukocytes to sites of inflammation, and lower susceptibility to sepsis. These studies demonstrate that macrophage RXRα plays key roles in the regulation of innate immunity and represents a potential target for immunotherapy of sepsis.
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RXRα homodimers can also regulate gene transcription.
“Recent data showed that RXRα homodimers can also regulate gene transcription36.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [36]
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Retinoid X receptors in macrophage biology
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- Authors
- Núñez, V., Alameda, D., Rico, D., Mota, R., Gonzalo, P., Cedenilla, M., Fischer, T., Boscá, L., Glass, C. K., Arroyo, A. G., & Ricote, M.
- Affiliations
- Spanish National Centre for Cardiovascular Research (ES)
- Departments of aRegenerative Cardiology and
- Centro Nacional de Biotecnología (ES)
- Consejo Superior de Investigaciones Científicas (ES)
- University of California System (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-05-24
- Volume
- 107
- Issue
- 23
- Pages
- 10626-10631
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2890831
- OpenAlex
- W2136706561
- Cited by
- 133
- References
- 42
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 7 · 2023: 9 · 2022: 14 · 2021: 13 · 2020: 13 · 2019: 7 · 2018: 7 · 2017: 5 · 2016: 8 · 2015: 10 · 2014: 6 · 2013: 9 · 2012: 5
- FWCI
- 3.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- retinoid X receptor alpha, macrophages, chemokine expression, CCL6, CCL9, innate immunity, inflammation, sepsis susceptibility, leukocyte recruitment, myeloid-specific knockout, nuclear receptor signaling, immunotherapy
- MeSH terms
- Animals, Base Sequence, Cells, Cultured, Immunity, Innate, Macrophages, Transcription, Genetic, Up-Regulation, Mice, Knockout, Sepsis, Macrophage Inflammatory Proteins, Chemokines, CC, Retinoid X Receptor alpha, Mice
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