The small chain fatty acid butyrate antagonizes the TCR-stimulation-induced metabolic shift in murine epidermal γδ T cells

Authors

  • Lukas Häselbarth IUF – Leibniz Research Institute for Environmental Medicine, Auf´m Hennekamp 50, 40225 Düsseldorf, Germany
  • D. Margriet Ouwens German Diabetes Research Center, Auf´m Hennekamp 65, 40225 Düsseldorf, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany; Department of Endocrinology, Ghent University Hospital, Ghent, Belgium
  • Nadine Teichweyde IUF – Leibniz Research Institute for Environmental Medicine, Auf´m Hennekamp 50, 40225 Düsseldorf, Germany
  • Katrin Hochrath IUF – Leibniz Research Institute for Environmental Medicine, Auf´m Hennekamp 50, 40225 Düsseldorf, Germany
  • Katja Merches IUF – Leibniz Research Institute for Environmental Medicine, Auf´m Hennekamp 50, 40225 Düsseldorf, Germany
  • Charlotte Esser IUF – Leibniz Research Institute for Environmental Medicine, Auf´m Hennekamp 50, 40225 Düsseldorf, Germany, Phone +49 211 3389 253, E-mail: chesser@uni-duesseldorf.de

DOI:

https://doi.org/10.17179/excli2020-1123

Keywords:

dendritic epidermal T cells, metabolism, short chain fatty acids, butyrate, propionate, acetate

Abstract

The metabolic requirements change during cell proliferation and differentiation. Upon antigen-stimulation, effector T cells switch from adenosine-triphospate (ATP)-production by oxidative phosphorylation in the mitochondria to glycolysis. In the gut it was shown that short chain fatty acids (SCFA), fermentation products of the microbiota in colon, ameliorate inflammatory reactions by supporting the differentiation of regulatory T cells. SCFA are a major energy source, but they are also anabolic metabolites, histone-deacetylase-inhibitors and activators of G protein receptors. Recently, it was reported that a topical application of the SCFA butyrate promotes regulatory T cells in the skin. Here we ask if the SCFA butyrate, propionate and acetate affect the energy metabolism and inflammatory potential of dendritic epidermal T cells (DETC), the innate resident skin γδ T cell population. Using the Seahorse™ technology, we measured glycolysis and oxidative phosphorylation (OXPHOS) in a murine DETC cell line, 7-17, upon TCR-stimulation by CD3/CD28 crosslinking, with or without SCFA addition. TCR engagement resulted in a change of the ratio glycolysis/OXPHOS. A similar metabolic shift has been described for activated CD4 T cells. Addition of 5 mM SCFA, in particular butyrate, antagonized the effect. Stimulated DETC secrete cytokines, e.g. the pro-inflammatory cytokine interferon-gamma (IFNγ), and thereby regulate skin homeostasis. Addition of butyrate and propionate to the cultures at non-toxic concentrations decreased secretion of IFNγ by DETC and increased the expression of the immunoregulatory surface receptor CD69. We hypothesize that SCFA can dampen the inflammatory activity of DETC.

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Published

2020-03-09

How to Cite

Häselbarth, L., Ouwens, D. M., Teichweyde, N., Hochrath, K., Merches, K., & Esser, C. (2020). The small chain fatty acid butyrate antagonizes the TCR-stimulation-induced metabolic shift in murine epidermal γδ T cells. EXCLI Journal, 19, 334–350. https://doi.org/10.17179/excli2020-1123

Issue

Vol. 19 (2020)

Section

Original articles

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