B cell-intrinsic epigenetic modulation of antibody responses by dietary fiber-derived short-chain fatty acids
Open Access
- 2 January 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 11 (1), 1-19
- https://doi.org/10.1038/s41467-019-13603-6
Abstract
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.Keywords
Funding Information
- Alliance for Lupus Research (ALR 641363)
- U.S. Department of Health & Human Services | National Institutes of Health (R01 AI105813, R01 AI079705, T32 AI138944)
- U.S. Department of Health & Human Services | National Institutes of Health
- U.S. Department of Health & Human Services | National Institutes of Health
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