Butyrate increases IL-23 production by stimulated dendritic cells

Bradford E. Berndt, Min Zhang, Stephanie Y. Owyang, Tyler S. Cole, Teresa W. Wang, Jay Luther, Natalia A. Veniaminova, Juanita L. Merchant, Chun Chia Chen, Gary B. Huffnagle, John Y. Kao

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

The gut microbiota is essential for the maintenance of intestinal immune homeostasis and is responsible for breaking down dietary fiber into short-chain fatty acids (SCFAs). Butyrate, the most abundant bioactive SCFA in the gut, is a histone deacetylase inhibitor (HDACi), a class of drug that has potent immunomodulatory properties. This characteristic of butyrate, along with our previous discovery that conventional dendritic cells (DCs) are required for the development of experimental colitis, led us to speculate that butyrate may modulate DC function to regulate gut mucosal homeostasis. We found that butyrate, in addition to suppressing LPS-induced bone marrowderived DC maturation and inhibiting DC IL-12 production, significantly induced IL-23 expression. The upregulation of mRNA subunit IL-23p19 at the pretranslational level was consistent with the role of HDACi on the epigenetic modification of gene expression. Furthermore, the mechanism of IL-23p19 upregulation was independent of Stat3 and ZBP89. Coculture of splenocytes with LPS-stimulated DCs pretreated with or without butyrate was performed and showed a significant induction of IL-17 and IL-10. We demonstrated further the effect of butyrate in vivo using dextran sulfate sodium (DSS)-induced colitis and found that the addition of butyrate in the drinking water of mice worsened DSS-colitis. This is in contrast to the daily intraperitoneal butyrate injection of DSS-treated mice, which mildly improved disease severity. Our study highlights a novel effect of butyrate in upregulating IL-23 production of activated DCs and demonstrates a difference in the host response to the oral vs. systemic route of butyrate administration.

Original languageEnglish (US)
Pages (from-to)G1384-G1392
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume303
Issue number12
DOIs
StatePublished - Dec 15 2012
Externally publishedYes

Keywords

  • Immunoregulation
  • Inflammatory bowel disease basic research
  • Mucosal immunology
  • Short-chain fatty acids

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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