Ghrelin Inhibits the Differentiation of T Helper 17 cells through m TOR/STAT3 Signaling Pathway

【作者】 徐艳慧； 赵晶； 冯娟； 李茵； 张炜真；

【机构】 北京大学基础医学院生理学与病理生理学系；

【摘要】 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(m TOR)and signal transducer and activator of transcription 3(STAT3)was observed in the spleens of GHSR1a-/-mice.Activation of m TOR signaling by injection of Cre-expressiong adenovirus into tuberous sclerosis complex1(TSC1)loxp/loxp mice increased the differentiation of Th17 cells in spleen,which was associated with an enhanced and phosphorylation of STAT3.Activation of m TOR signaling by leucine or overexpression of p70 ribosome protein subunit 6 kinase 1(S6K1)activated m TOR signaling in isolated T cells.Reversed the ghrelin-induced inhibition of i Th17 cell differentiation.In conclusion,m TOR mediates the inhibitory effect of ghrelin on the differentiation of Th17 cells by interacting with STAT3.更多还原

【Abstract】 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(m TOR) and signal transducer and activator of transcription 3(STAT3) was observed in the spleens of GHSR1a-/-mice.Activation of m TOR 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 enhanced and phosphorylation of STAT3.Activation of m TOR signaling by leucine or overexpression of p70 ribosome protein subunit 6 kinase 1(S6K1) activated m TOR signaling in isolated T cells.Reversed the ghrelin-induced inhibition of i Th17 cell differentiation.In conclusion,m TOR mediates the inhibitory effect of ghrelin on the differentiation of Th17 cells by interacting with STAT3.更多还原