Science and Research

The Microbial Metabolite Butyrate Induces Expression of Th1-Associated Factors in CD4(+) T Cells

Short-chain fatty acids (SCFAs), which are generated by the bacterial fermentation of dietary fibers, promote expansion of regulatory T cells (Tregs). Potential therapeutic value of SCFAs has been recently highlighted in the experimental models of T cell-mediated autoimmunity and allergic inflammation. These studies suggest that physiological intestinal concentrations of SCFAs within the millimolar range are crucial for dampening inflammation-mediated processes. Here, we describe opposing effects of SCFAs on T cell-mediated immune responses. In accordance with published data, lower butyrate concentrations facilitated differentiation of Tregs in vitro and in vivo under steady-state conditions. In contrast, higher concentrations of butyrate induced expression of the transcription factor T-bet in all investigated T cell subsets resulting in IFN-gamma-producing Tregs or conventional T cells. This effect was mediated by the inhibition of histone deacetylase activity and was independent of SCFA-receptors FFA2 and FFA3 as well as of Na(+)-coupled SCFA transporter Slc5a8. Importantly, while butyrate was not able to induce the generation of Tregs in the absence of TGF-beta1, the expression of T-bet and IFN-gamma was triggered upon stimulation of CD4(+) T cells with this SCFA alone. Moreover, the treatment of germ-free mice with butyrate enhanced the expression of T-bet and IFN-gamma during acute colitis. Our data reveal that, depending on its concentration and immunological milieu, butyrate may exert either beneficial or detrimental effects on the mucosal immune system.

  • Kespohl, M.
  • Vachharajani, N.
  • Luu, M.
  • Harb, H.
  • Pautz, S.
  • Wolff, S.
  • Sillner, N.
  • Walker, A.
  • Schmitt-Kopplin, P.
  • Boettger, T.
  • Renz, H.
  • Offermanns, S.
  • Steinhoff, U.
  • Visekruna, A.

Keywords

  • butyrate
  • inhibition of histone deacetylase activity
  • interferon-gamma
  • regulatory T cells
  • short-chain fatty acids
Publication details
DOI: 10.3389/fimmu.2017.01036
Journal: Frontiers in immunology
Pages: 1036 
Work Type: Original
Location: UGMLC
Disease Area: AA, General Lung and Other
Partner / Member: MPI-BN, UMR
Access-Number: 28894447

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