Lactate induces metabolic and epigenetic reprogramming of pro‐inflammatory Th17 cells
| العنوان: | Lactate induces metabolic and epigenetic reprogramming of pro‐inflammatory Th17 cells |
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| المؤلفون: | Aleksandra Lopez Krol, Hannah P Nehring, Felix F Krause, Anne Wempe, Hartmann Raifer, Andrea Nist, Thorsten Stiewe, Wilhelm Bertrams, Bernd Schmeck, Maik Luu, Hanna Leister, Ho‐Ryun Chung, Uta‐Maria Bauer, Till Adhikary, Alexander Visekruna |
| المصدر: | EMBO reports. 23 |
| بيانات النشر: | EMBO, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Genetics, Molecular Biology, Biochemistry |
| الوصف: | Increased lactate levels in the tissue microenvironment are a well-known feature of chronic inflammation. However, the role of lactate in regulating T cell function remains controversial. Here, we demonstrate that extracellular lactate predominantly induces deregulation of the Th17-specific gene expression program by modulating the metabolic and epigenetic status of Th17 cells. Following lactate treatment, Th17 cells significantly reduced their IL-17A production and upregulated Foxp3 expression through ROS-driven IL-2 secretion. Moreover, we observed increased levels of genome-wide histone H3K18 lactylation, a recently described marker for active chromatin in macrophages, in lactate-treated Th17 cells. In addition, we show that high lactate concentrations suppress Th17 pathogenicity during intestinal inflammation in mice. These results indicate that lactate is capable of reprogramming pro-inflammatory T cell phenotypes into regulatory T cells. |
| تدمد: | 1469-3178 1469-221X |
| DOI: | 10.15252/embr.202254685 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a049f76bbaed8cb91cd9740cbed78366 https://doi.org/10.15252/embr.202254685 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....a049f76bbaed8cb91cd9740cbed78366 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14693178 1469221X |
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| DOI: | 10.15252/embr.202254685 |