Cargando…

Glucocorticoid receptor promotes the function of myeloid-derived suppressor cells by suppressing HIF1α-dependent glycolysis

Immunomodulatory signaling imposes tight regulations on metabolic programs within immune cells and consequentially determines immune response outcomes. Although the glucocorticoid receptor (GR) has been recently implicated in regulating the function of myeloid-derived suppressor cells (MDSCs), wheth...

Descripción completa

Detalles Bibliográficos
Autores principales: Lu, Yun, Liu, Huanrong, Bi, Yujing, Yang, Hui, Li, Yan, Wang, Jian, Zhang, Zhengguo, Wang, Yu, Li, Chunxiao, Jia, Anna, Han, Linian, Hu, Ying, Zhao, Yong, Wang, Ruoning, Liu, Guangwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079089/
https://www.ncbi.nlm.nih.gov/pubmed/28287112
http://dx.doi.org/10.1038/cmi.2017.5
_version_ 1783345206210330624
author Lu, Yun
Liu, Huanrong
Bi, Yujing
Yang, Hui
Li, Yan
Wang, Jian
Zhang, Zhengguo
Wang, Yu
Li, Chunxiao
Jia, Anna
Han, Linian
Hu, Ying
Zhao, Yong
Wang, Ruoning
Liu, Guangwei
author_facet Lu, Yun
Liu, Huanrong
Bi, Yujing
Yang, Hui
Li, Yan
Wang, Jian
Zhang, Zhengguo
Wang, Yu
Li, Chunxiao
Jia, Anna
Han, Linian
Hu, Ying
Zhao, Yong
Wang, Ruoning
Liu, Guangwei
author_sort Lu, Yun
collection PubMed
description Immunomodulatory signaling imposes tight regulations on metabolic programs within immune cells and consequentially determines immune response outcomes. Although the glucocorticoid receptor (GR) has been recently implicated in regulating the function of myeloid-derived suppressor cells (MDSCs), whether the dysregulation of GR in MDSCs is involved in immune-mediated hepatic diseases and how GR regulates the function of MDSCs in such a context remains unknown. Here, we revealed the dysregulation of GR expression in MDSCs during innate immunological hepatic injury (IMH) and found that GR regulates the function of MDSCs through modulating HIF1α-dependent glycolysis. Pharmacological modulation of GR by its agonist (dexamethasone, Dex) protects IMH mice against inflammatory injury. Mechanistically, GR signaling suppresses HIF1α and HIF1α-dependent glycolysis in MDSCs and thus promotes the immune suppressive activity of MDSCs. Our studies reveal a role of GR-HIF1α in regulating the metabolism and function of MDSCs and further implicate MDSC GR signaling as a potential therapeutic target in hepatic diseases that are driven by innate immune cell-mediated systemic inflammation.
format Online
Article
Text
id pubmed-6079089
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-60790892018-08-07 Glucocorticoid receptor promotes the function of myeloid-derived suppressor cells by suppressing HIF1α-dependent glycolysis Lu, Yun Liu, Huanrong Bi, Yujing Yang, Hui Li, Yan Wang, Jian Zhang, Zhengguo Wang, Yu Li, Chunxiao Jia, Anna Han, Linian Hu, Ying Zhao, Yong Wang, Ruoning Liu, Guangwei Cell Mol Immunol Article Immunomodulatory signaling imposes tight regulations on metabolic programs within immune cells and consequentially determines immune response outcomes. Although the glucocorticoid receptor (GR) has been recently implicated in regulating the function of myeloid-derived suppressor cells (MDSCs), whether the dysregulation of GR in MDSCs is involved in immune-mediated hepatic diseases and how GR regulates the function of MDSCs in such a context remains unknown. Here, we revealed the dysregulation of GR expression in MDSCs during innate immunological hepatic injury (IMH) and found that GR regulates the function of MDSCs through modulating HIF1α-dependent glycolysis. Pharmacological modulation of GR by its agonist (dexamethasone, Dex) protects IMH mice against inflammatory injury. Mechanistically, GR signaling suppresses HIF1α and HIF1α-dependent glycolysis in MDSCs and thus promotes the immune suppressive activity of MDSCs. Our studies reveal a role of GR-HIF1α in regulating the metabolism and function of MDSCs and further implicate MDSC GR signaling as a potential therapeutic target in hepatic diseases that are driven by innate immune cell-mediated systemic inflammation. Nature Publishing Group UK 2017-03-13 2018-06 /pmc/articles/PMC6079089/ /pubmed/28287112 http://dx.doi.org/10.1038/cmi.2017.5 Text en © The Chinese Society of Immunology and The University of Science and Technology of China, All rights reserved 2017 This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
spellingShingle Article
Lu, Yun
Liu, Huanrong
Bi, Yujing
Yang, Hui
Li, Yan
Wang, Jian
Zhang, Zhengguo
Wang, Yu
Li, Chunxiao
Jia, Anna
Han, Linian
Hu, Ying
Zhao, Yong
Wang, Ruoning
Liu, Guangwei
Glucocorticoid receptor promotes the function of myeloid-derived suppressor cells by suppressing HIF1α-dependent glycolysis
title Glucocorticoid receptor promotes the function of myeloid-derived suppressor cells by suppressing HIF1α-dependent glycolysis
title_full Glucocorticoid receptor promotes the function of myeloid-derived suppressor cells by suppressing HIF1α-dependent glycolysis
title_fullStr Glucocorticoid receptor promotes the function of myeloid-derived suppressor cells by suppressing HIF1α-dependent glycolysis
title_full_unstemmed Glucocorticoid receptor promotes the function of myeloid-derived suppressor cells by suppressing HIF1α-dependent glycolysis
title_short Glucocorticoid receptor promotes the function of myeloid-derived suppressor cells by suppressing HIF1α-dependent glycolysis
title_sort glucocorticoid receptor promotes the function of myeloid-derived suppressor cells by suppressing hif1α-dependent glycolysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079089/
https://www.ncbi.nlm.nih.gov/pubmed/28287112
http://dx.doi.org/10.1038/cmi.2017.5
work_keys_str_mv AT luyun glucocorticoidreceptorpromotesthefunctionofmyeloidderivedsuppressorcellsbysuppressinghif1adependentglycolysis
AT liuhuanrong glucocorticoidreceptorpromotesthefunctionofmyeloidderivedsuppressorcellsbysuppressinghif1adependentglycolysis
AT biyujing glucocorticoidreceptorpromotesthefunctionofmyeloidderivedsuppressorcellsbysuppressinghif1adependentglycolysis
AT yanghui glucocorticoidreceptorpromotesthefunctionofmyeloidderivedsuppressorcellsbysuppressinghif1adependentglycolysis
AT liyan glucocorticoidreceptorpromotesthefunctionofmyeloidderivedsuppressorcellsbysuppressinghif1adependentglycolysis
AT wangjian glucocorticoidreceptorpromotesthefunctionofmyeloidderivedsuppressorcellsbysuppressinghif1adependentglycolysis
AT zhangzhengguo glucocorticoidreceptorpromotesthefunctionofmyeloidderivedsuppressorcellsbysuppressinghif1adependentglycolysis
AT wangyu glucocorticoidreceptorpromotesthefunctionofmyeloidderivedsuppressorcellsbysuppressinghif1adependentglycolysis
AT lichunxiao glucocorticoidreceptorpromotesthefunctionofmyeloidderivedsuppressorcellsbysuppressinghif1adependentglycolysis
AT jiaanna glucocorticoidreceptorpromotesthefunctionofmyeloidderivedsuppressorcellsbysuppressinghif1adependentglycolysis
AT hanlinian glucocorticoidreceptorpromotesthefunctionofmyeloidderivedsuppressorcellsbysuppressinghif1adependentglycolysis
AT huying glucocorticoidreceptorpromotesthefunctionofmyeloidderivedsuppressorcellsbysuppressinghif1adependentglycolysis
AT zhaoyong glucocorticoidreceptorpromotesthefunctionofmyeloidderivedsuppressorcellsbysuppressinghif1adependentglycolysis
AT wangruoning glucocorticoidreceptorpromotesthefunctionofmyeloidderivedsuppressorcellsbysuppressinghif1adependentglycolysis
AT liuguangwei glucocorticoidreceptorpromotesthefunctionofmyeloidderivedsuppressorcellsbysuppressinghif1adependentglycolysis