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Pharmacological modulation and genetic deletion of REV-ERBα and REV-ERBβ regulates dendritic cell development.
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- Author(s): Amir, Mohammed1 (AUTHOR); Campbell, Sean1 (AUTHOR); Kamenecka, Theodore M.2 (AUTHOR); Solt, Laura A.1,2 (AUTHOR)
- Source:
Biochemical & Biophysical Research Communications. Jul2020, Vol. 527 Issue 4, p1000-1007. 8p.- Subject Terms:
- Source:
- Additional Information
- Abstract: The nuclear receptors REV-ERBα and REV-ERBβ have been demonstrated to play key roles in the regulation of numerous physiological functions, such as metabolism and the circadian rhythm. Recent studies have established the REV-ERBs' roles in immunity, including macrophage and T cell responses. In contrast, their roles in dendritic cells have not been well defined. Dendritic cells are potent antigen presenting cells, connecting microbial sensing and innate immunity to adaptive immune responses. We demonstrate that both REV-ERBα and REV-ERBβ expression is upregulated during the course of bone marrow derived dendritic cell (BMDC) differentiation. BMDCs from REV-ERBα and REV-ERBβ deficient mice showed enhanced expression of maturation markers like CD86, MHCII, and proinflammatory cytokines. Conversely, treatment of BMDCs with a REV-ERB-specific agonist, SR9009, inhibited the expression of maturation markers and proinflammatory cytokines. Our study suggests the REV-ERBs act as negative regulators of dendritic cell development and activation. These results indicate that pharmacological modulation of REV-ERB activity could be an attractive strategy to modulate DC activation status and for DC-based therapies. • The REV-ERBs are upregulated during BMDC development. • The REV-ERBs regulate MHCII and CD86 surface expression in BMDCs. • The REV-ERBs act as negative regulators of BMDC pro-inflammatory cytokine gene expression. • Small molecule modulation of REV-ERB activity affects BMDC maturation and gene expression. [ABSTRACT FROM AUTHOR]
- Abstract: Copyright of Biochemical & Biophysical Research Communications is the property of Academic Press Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Abstract:
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