Pharmacological modulation and genetic deletion of REV-ERBα and REV-ERBß regulates dendritic cell development.
Biochem Biophys Res Commun
; 527(4): 1000-1007, 2020 07 05.
Article
em En
| MEDLINE
| ID: mdl-32439175
ABSTRACT
The nuclear receptors REV-ERBα and REV-ERBß 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-ERBß expression is upregulated during the course of bone marrow derived dendritic cell (BMDC) differentiation. BMDCs from REV-ERBα and REV-ERBß 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.
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MEDLINE
Assunto principal:
Proteínas Repressoras
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Células Dendríticas
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Células da Medula Óssea
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Deleção de Genes
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Receptores Citoplasmáticos e Nucleares
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Regulação da Expressão Gênica no Desenvolvimento
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Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article