Nature communications, 2020-01, Vol.11 (1), p.60-19, Article 60
2020
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- B cell-intrinsic epigenetic modulation of antibody responses by dietary fiber-derived short-chain fatty acids
- Ist Teil von
- Nature communications, 2020-01, Vol.11 (1), p.60-19, Article 60
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2020
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Short-chain fatty acids (SCFAs) butyrate and propionate are metabolites from dietary fiber's fermentation by gut microbiota that can affect differentiation or functions of T cells, macrophages and dendritic cells. We show here that at low doses these SCFAs directly impact B cell intrinsic functions to moderately enhance class-switch DNA recombination (CSR), while decreasing at higher doses over a broad physiological range, AID and Blimp1 expression, CSR, somatic hypermutation and plasma cell differentiation. In human and mouse B cells, butyrate and propionate decrease B cell Aicda and Prdm1 by upregulating select miRNAs that target Aicda and Prdm1 mRNA-3'UTRs through inhibition of histone deacetylation (HDAC) of those miRNA host genes. By acting as HDAC inhibitors, not as energy substrates or through GPR-engagement signaling in these B cell-intrinsic processes, these SCFAs impair intestinal and systemic T-dependent and T-independent antibody responses. Their epigenetic impact on B cells extends to inhibition of autoantibody production and autoimmunity in mouse lupus models.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-019-13603-6Titel-ID: cdi_doaj_primary_oai_doaj_org_article_ce20bc7d054049c9aaae3302f0ad4e24
- Format
- –
- Schlagworte
- Animal models, Animals, Antibodies, Antibodies - genetics, Antibodies - immunology, Antibodies - metabolism, Autoantibodies, Autoantibodies - genetics, Autoantibodies - immunology, Autoimmunity, B-Lymphocytes - drug effects, B-Lymphocytes - immunology, Butyrates - pharmacology, Cell differentiation, Class switching, Cytidine Deaminase - antagonists & inhibitors, Cytidine Deaminase - genetics, Cytidine Deaminase - immunology, Cytidine Deaminase - metabolism, Deacetylation, Dendritic cells, Deoxyribonucleic acid, Dietary Fiber, Differentiation (biology), DNA, Energy resources, Epigenesis, Genetic - drug effects, Epigenetics, Fatty acids, Fatty Acids, Volatile - isolation & purification, Fatty Acids, Volatile - pharmacokinetics, Fatty Acids, Volatile - pharmacology, Female, Fermentation, Gastrointestinal Microbiome - drug effects, Gastrointestinal Microbiome - genetics, Gastrointestinal Microbiome - immunology, Histone deacetylase, Histone Deacetylase Inhibitors - immunology, Histone Deacetylase Inhibitors - pharmacology, Humans, Intestinal microflora, Intestine, Lupus Erythematosus, Systemic - drug therapy, Lupus Erythematosus, Systemic - immunology, Lymphocytes, Lymphocytes B, Lymphocytes T, Macrophages, Metabolites, Mice, Inbred C57BL, Mice, Mutant Strains, Microbiota, miRNA, mRNA, Positive Regulatory Domain I-Binding Factor 1 - antagonists & inhibitors, Positive Regulatory Domain I-Binding Factor 1 - genetics, Positive Regulatory Domain I-Binding Factor 1 - immunology, Positive Regulatory Domain I-Binding Factor 1 - metabolism, Propionates - pharmacology, Propionic acid, Recombination, Somatic hypermutation, Substrate inhibition, Tissue Distribution