Ghrelin inhibits the differentiation of T helper 17 cells through mTOR/STAT3 signaling pathway.

Enhanced activity of interleukin 17 (IL-17) producing T helper 17 (Th17) cells plays an important role in autoimmune and inflammatory diseases. Significant loss of body weight and appetite is associated with chronic inflammation and immune activation, suggesting the cross talk between immune and neu...

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Main Authors: Yanhui Xu, Ziru Li, Yue Yin, He Lan, Jun Wang, Jing Zhao, Juan Feng, Yin Li, Weizhen Zhang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4319964?pdf=render
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author Yanhui Xu
Ziru Li
Yue Yin
He Lan
Jun Wang
Jing Zhao
Juan Feng
Yin Li
Weizhen Zhang
author_facet Yanhui Xu
Ziru Li
Yue Yin
He Lan
Jun Wang
Jing Zhao
Juan Feng
Yin Li
Weizhen Zhang
author_sort Yanhui Xu
collection DOAJ
description Enhanced activity of interleukin 17 (IL-17) producing T helper 17 (Th17) cells plays an important role in autoimmune and inflammatory diseases. Significant loss of body weight and appetite is associated with chronic inflammation and immune activation, suggesting the cross talk between immune and neuroendocrine systems. Ghrelin has been shown to regulate the organism immune function. However, the effects of ghrelin on the differentiation of Th17 cells remain elusive. In the present study, we observed the enhanced differentiation of Th17 cells in spleens of growth hormone secretagogue receptor 1a (GHSR1a)-/- mice. Treatment of ghrelin repressed Th17 cell differentiation in a time- and concentration-dependent manner. Phosphorylation of mammalian target of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3) was increased in the spleens of GHSR1a-/- mice. Activation of mTOR signaling by injection of Cre-expressiong adenovirus into tuberous sclerosis complex 1 (TSC1) loxp/loxp mice increased the differentiation of Th17 cells in spleen, which was associated with an increment in the phosphorylation of STAT3. Activation of mTOR signaling by leucine or overexpression of p70 ribosome protein subunit 6 kinase 1 (S6K1) activated mTOR signaling in isolated T cells, while reversed the ghrelin-induced inhibition of iTh17 cell differentiation. In conclusion, mTOR mediates the inhibitory effect of ghrelin on the differentiation of Th17 cells by interacting with STAT3.
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spelling doaj.art-d664b1949c8a4a06841ab77fb3c39df02022-12-21T19:56:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01102e011708110.1371/journal.pone.0117081Ghrelin inhibits the differentiation of T helper 17 cells through mTOR/STAT3 signaling pathway.Yanhui XuZiru LiYue YinHe LanJun WangJing ZhaoJuan FengYin LiWeizhen ZhangEnhanced activity of interleukin 17 (IL-17) producing T helper 17 (Th17) cells plays an important role in autoimmune and inflammatory diseases. Significant loss of body weight and appetite is associated with chronic inflammation and immune activation, suggesting the cross talk between immune and neuroendocrine systems. Ghrelin has been shown to regulate the organism immune function. However, the effects of ghrelin on the differentiation of Th17 cells remain elusive. In the present study, we observed the enhanced differentiation of Th17 cells in spleens of growth hormone secretagogue receptor 1a (GHSR1a)-/- mice. Treatment of ghrelin repressed Th17 cell differentiation in a time- and concentration-dependent manner. Phosphorylation of mammalian target of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3) was increased in the spleens of GHSR1a-/- mice. Activation of mTOR signaling by injection of Cre-expressiong adenovirus into tuberous sclerosis complex 1 (TSC1) loxp/loxp mice increased the differentiation of Th17 cells in spleen, which was associated with an increment in the phosphorylation of STAT3. Activation of mTOR signaling by leucine or overexpression of p70 ribosome protein subunit 6 kinase 1 (S6K1) activated mTOR signaling in isolated T cells, while reversed the ghrelin-induced inhibition of iTh17 cell differentiation. In conclusion, mTOR mediates the inhibitory effect of ghrelin on the differentiation of Th17 cells by interacting with STAT3.http://europepmc.org/articles/PMC4319964?pdf=render
spellingShingle Yanhui Xu
Ziru Li
Yue Yin
He Lan
Jun Wang
Jing Zhao
Juan Feng
Yin Li
Weizhen Zhang
Ghrelin inhibits the differentiation of T helper 17 cells through mTOR/STAT3 signaling pathway.
PLoS ONE
title Ghrelin inhibits the differentiation of T helper 17 cells through mTOR/STAT3 signaling pathway.
title_full Ghrelin inhibits the differentiation of T helper 17 cells through mTOR/STAT3 signaling pathway.
title_fullStr Ghrelin inhibits the differentiation of T helper 17 cells through mTOR/STAT3 signaling pathway.
title_full_unstemmed Ghrelin inhibits the differentiation of T helper 17 cells through mTOR/STAT3 signaling pathway.
title_short Ghrelin inhibits the differentiation of T helper 17 cells through mTOR/STAT3 signaling pathway.
title_sort ghrelin inhibits the differentiation of t helper 17 cells through mtor stat3 signaling pathway
url http://europepmc.org/articles/PMC4319964?pdf=render
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