Title |
The Microbial Metabolite Butyrate Induces Expression of Th1-Associated Factors in CD4+ T Cells
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Published in |
Frontiers in immunology, August 2017
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DOI | 10.3389/fimmu.2017.01036 |
Pubmed ID | |
Authors |
Meike Kespohl, Niyati Vachharajani, Maik Luu, Hani Harb, Sabine Pautz, Svenja Wolff, Nina Sillner, Alesia Walker, Philippe Schmitt-Kopplin, Thomas Boettger, Harald Renz, Stefan Offermanns, Ulrich Steinhoff, Alexander Visekruna |
Abstract |
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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Geographical breakdown
Country | Count | As % |
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United Kingdom | 3 | 27% |
Australia | 1 | 9% |
France | 1 | 9% |
Mexico | 1 | 9% |
Malaysia | 1 | 9% |
Switzerland | 1 | 9% |
Spain | 1 | 9% |
Unknown | 2 | 18% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 10 | 91% |
Scientists | 1 | 9% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 219 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 40 | 18% |
Student > Bachelor | 25 | 11% |
Researcher | 23 | 11% |
Student > Master | 20 | 9% |
Other | 11 | 5% |
Other | 33 | 15% |
Unknown | 67 | 31% |
Readers by discipline | Count | As % |
---|---|---|
Immunology and Microbiology | 35 | 16% |
Biochemistry, Genetics and Molecular Biology | 33 | 15% |
Medicine and Dentistry | 17 | 8% |
Agricultural and Biological Sciences | 12 | 5% |
Nursing and Health Professions | 7 | 3% |
Other | 35 | 16% |
Unknown | 80 | 37% |