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B cell-intrinsic epigenetic modulation of antibody responses by dietary fiber-derived short-chain fatty acids.


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.

SUBMITTER: Sanchez HN 

PROVIDER: S-EPMC6940392 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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B cell-intrinsic epigenetic modulation of antibody responses by dietary fiber-derived short-chain fatty acids.

Sanchez Helia N HN   Moroney Justin B JB   Gan Huoqun H   Shen Tian T   Im John L JL   Li Tianbao T   Taylor Julia R JR   Zan Hong H   Casali Paolo P  

Nature communications 20200102 1


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 dif  ...[more]

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