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Butyrate limits human natural killer cell effector function
The gut microbiota regulates chronic inflammation and has been implicated in the pathogenesis of a broad spectrum of disease including autoimmunity and cancer. Microbial short-chain fatty acids (SCFAs) e.g., butyrate have demonstrated immunomodulatory effects and are thought to be key mediators of t...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9932090/ https://www.ncbi.nlm.nih.gov/pubmed/36792800 http://dx.doi.org/10.1038/s41598-023-29731-5 |
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author | Zaiatz-Bittencourt, Vanessa Jones, Fiona Tosetto, Miriam Scaife, Caitriona Cagney, Gerard Jones, Evan Doherty, Glen A. Ryan, Elizabeth J. |
author_facet | Zaiatz-Bittencourt, Vanessa Jones, Fiona Tosetto, Miriam Scaife, Caitriona Cagney, Gerard Jones, Evan Doherty, Glen A. Ryan, Elizabeth J. |
author_sort | Zaiatz-Bittencourt, Vanessa |
collection | PubMed |
description | The gut microbiota regulates chronic inflammation and has been implicated in the pathogenesis of a broad spectrum of disease including autoimmunity and cancer. Microbial short-chain fatty acids (SCFAs) e.g., butyrate have demonstrated immunomodulatory effects and are thought to be key mediators of the host-microbiome interaction. Here, we investigated the effect of butyrate on effector functions of blood derived human NK cells stimulated for 18 h with a combination of IL-12/IL-15, a potent mix of cytokines that drive NK cell activation. We show that butyrate has a strong anti-inflammatory effect on NK cells. NK cells cultured in the presence of butyrate expressed lower levels of activating receptors (TRAIL, NKp30, NKp44) and produced lower levels of cytokines (IFNγ, TNF-α, IL-22, granzyme B, granzyme A, perforin) in response to IL-12/IL-15. Butyrate restricted NK cell function by downregulation of mTORC1 activity, c-Myc mRNA expression and metabolism. Using a shotgun proteomic approach, we confirmed the effect of butyrate on NK cell cytokine signaling and metabolism and identified BRD2, MAT2A and EHD1 as downstream mediators of these effects. This insight into the immunomodulatory activity of butyrate on human NK cell function might help to develop new ways to limit NK cell function during chronic inflammation. |
format | Online Article Text |
id | pubmed-9932090 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-99320902023-02-17 Butyrate limits human natural killer cell effector function Zaiatz-Bittencourt, Vanessa Jones, Fiona Tosetto, Miriam Scaife, Caitriona Cagney, Gerard Jones, Evan Doherty, Glen A. Ryan, Elizabeth J. Sci Rep Article The gut microbiota regulates chronic inflammation and has been implicated in the pathogenesis of a broad spectrum of disease including autoimmunity and cancer. Microbial short-chain fatty acids (SCFAs) e.g., butyrate have demonstrated immunomodulatory effects and are thought to be key mediators of the host-microbiome interaction. Here, we investigated the effect of butyrate on effector functions of blood derived human NK cells stimulated for 18 h with a combination of IL-12/IL-15, a potent mix of cytokines that drive NK cell activation. We show that butyrate has a strong anti-inflammatory effect on NK cells. NK cells cultured in the presence of butyrate expressed lower levels of activating receptors (TRAIL, NKp30, NKp44) and produced lower levels of cytokines (IFNγ, TNF-α, IL-22, granzyme B, granzyme A, perforin) in response to IL-12/IL-15. Butyrate restricted NK cell function by downregulation of mTORC1 activity, c-Myc mRNA expression and metabolism. Using a shotgun proteomic approach, we confirmed the effect of butyrate on NK cell cytokine signaling and metabolism and identified BRD2, MAT2A and EHD1 as downstream mediators of these effects. This insight into the immunomodulatory activity of butyrate on human NK cell function might help to develop new ways to limit NK cell function during chronic inflammation. Nature Publishing Group UK 2023-02-15 /pmc/articles/PMC9932090/ /pubmed/36792800 http://dx.doi.org/10.1038/s41598-023-29731-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Zaiatz-Bittencourt, Vanessa Jones, Fiona Tosetto, Miriam Scaife, Caitriona Cagney, Gerard Jones, Evan Doherty, Glen A. Ryan, Elizabeth J. Butyrate limits human natural killer cell effector function |
title | Butyrate limits human natural killer cell effector function |
title_full | Butyrate limits human natural killer cell effector function |
title_fullStr | Butyrate limits human natural killer cell effector function |
title_full_unstemmed | Butyrate limits human natural killer cell effector function |
title_short | Butyrate limits human natural killer cell effector function |
title_sort | butyrate limits human natural killer cell effector function |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9932090/ https://www.ncbi.nlm.nih.gov/pubmed/36792800 http://dx.doi.org/10.1038/s41598-023-29731-5 |
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