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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.*

The microbial metabolite butyrate induces expression of Th1- associated factors in cD4+ T cells.

Front. Immunol. 8:1036 (2017)
Verlagsversion Forschungsdaten DOI
Open Access Gold
Creative Commons Lizenzvertrag
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-γ-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-β1, the expression of T-bet and IFN-γ 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-γ 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Butyrate ; Inhibition Of Histone Deacetylase Activity ; Interferon-gamma ; Regulatory T Cells ; Short-chain Fatty Acids; Chain Fatty-acids; Histone Acetylation; Deacetylase Inhibition; C-rel; Induction; Differentiation; Fiber; Generation; Colitis
ISSN (print) / ISBN 1664-3224
e-ISSN 1664-3224
Quellenangaben Band: 8, Heft: , Seiten: , Artikelnummer: 1036 Supplement: ,
Verlag Frontiers
Verlagsort Lausanne
Begutachtungsstatus Peer reviewed