Vitamin B12 attenuates leukocyte inflammatory signature in COVID-19 via methyl-dependent changes in epigenetic markings

Frontiers in Immunology

Immunology

Gloria R. Franco¹  Vânia D’Almeida²  Vanessa Cavalcante-Silva²  Cristianne G. Cardoso³  Bárbara V. O. Prado³  Saionara C. Francisco³  Roney S. Coimbra⁴  Marina S. Oliveira⁴  Larissa M. G. Cassiano⁵  Anna C. M. Salim⁶ 

[1] Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil;Departamento de Psicobiologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil;Hospital Metropolitano Dr. Célio de Castro, Belo Horizonte, Brazil;Neurogenômica, Imunopatologia, Instituto René Rachou, Fiocruz, Belo Horizonte, Brazil;Neurogenômica, Imunopatologia, Instituto René Rachou, Fiocruz, Belo Horizonte, Brazil;Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil;Plataforma de Sequenciamento NGS (Next Generation Sequencing), Instituto René Rachou, Fiocruz, Belo Horizonte, Brazil;

关键词: COVID-19;    vitamin B12;    epidrugs;    chromatin remodeling;    DNA methylation;    epigenetic markings;    inflammation;    antiviral response;   

DOI  :  10.3389/fimmu.2023.1048790

 received in 2022-09-21, accepted in 2023-02-27,  发布年份 2023

来源: Frontiers

【 摘 要 】

COVID-19 induces chromatin remodeling in host immune cells, and it had previously been shown that vitamin B12 downregulates some inflammatory genes via methyl-dependent epigenetic mechanisms. In this work, whole blood cultures from moderate or severe COVID-19 patients were used to assess the potential of B12 as adjuvant drug. The vitamin normalized the expression of a panel of inflammatory genes still dysregulated in the leukocytes despite glucocorticoid therapy during hospitalization. B12 also increased the flux of the sulfur amino acid pathway, that regulates the bioavailability of methyl. Accordingly, B12-induced downregulation of CCL3 strongly and negatively correlated with the hypermethylation of CpGs in its regulatory regions. Transcriptome analysis revealed that B12 attenuates the effects of COVID-19 on most inflammation-related pathways affected by the disease. As far as we are aware, this is the first study to demonstrate that pharmacological modulation of epigenetic markings in leukocytes favorably regulates central components of COVID-19 physiopathology.

【 授权许可】

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Copyright © 2023 Cassiano, Cavalcante-Silva, Oliveira, Prado, Cardoso, Salim, Franco, D’Almeida, Francisco and Coimbra