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

Helia N. Sanchez, Justin B. Moroney, Huoqun Gan, Tian Shen, John L. Im, Tianbao Li, Julia R. Taylor, Hong Zan, Paolo Casali

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number60
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Dec 1 2020

Fingerprint

Volatile Fatty Acids
Dietary Fiber
fatty acids
antibodies
Epigenomics
Antibody Formation
B-Lymphocytes
Cells
Modulation
modulation
fibers
Antibodies
Butyrates
Propionates
MicroRNAs
Histones
Genetic Recombination
mice
Switches
Ground penetrating radar systems

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

B cell-intrinsic epigenetic modulation of antibody responses by dietary fiber-derived short-chain fatty acids. / Sanchez, Helia N.; Moroney, Justin B.; Gan, Huoqun; Shen, Tian; Im, John L.; Li, Tianbao; Taylor, Julia R.; Zan, Hong; Casali, Paolo.

In: Nature communications, Vol. 11, No. 1, 60, 01.12.2020.

Research output: Contribution to journalArticle

Sanchez, Helia N. ; Moroney, Justin B. ; Gan, Huoqun ; Shen, Tian ; Im, John L. ; Li, Tianbao ; Taylor, Julia R. ; Zan, Hong ; Casali, Paolo. / B cell-intrinsic epigenetic modulation of antibody responses by dietary fiber-derived short-chain fatty acids. In: Nature communications. 2020 ; Vol. 11, No. 1.
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