Butyrate increases IL-23 production by stimulated dendritic cells

• DOI: 10.1152/ajpgi.00540.2011
• Publication Date: 2012-10-20T01:21:19Z
• Authors: Bradford E. Berndt; Min Zhang; Stephanie Y. Owyang; Tyler S. Cole; Teresa W. Wang; Jay Luther; Natalia A. Veniam...; Juanita L. Merchant; Chun-Chia Chen; Gary B. Huffnagle; John Y. Kao
• Keywords: Sodium butyrate

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