title: Ghrelin inhibits the differentiation of T helper 17 cells through mTOR/STAT3 signaling pathway.
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 (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.
authors: Department of Physiology and Pathophysiology, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China.
authors: Yanhui
authors: Y
authors: Xu
authors: Department of Physiology and Pathophysiology, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China.
authors: Ziru
authors: Z
authors: Li
authors: Department of Physiology and Pathophysiology, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China.
authors: Yue
authors: Y
authors: Yin
authors: Department of Physiology and Pathophysiology, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China.
authors: He
authors: H
authors: Lan
authors: Department of Physiology and Pathophysiology, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China.
authors: Jun
authors: J
authors: Wang
authors: Department of Physiology and Pathophysiology, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China.
authors: Jing
authors: J
authors: Zhao
authors: Department of Physiology and Pathophysiology, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China.
authors: Juan
authors: J
authors: Feng
authors: Department of Physiology and Pathophysiology, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China.
authors: Yin
authors: Y
authors: Li
authors: Department of Physiology and Pathophysiology, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China; Department of Surgery, University of Michigan, Ann Arbor, MI, United States of America.
authors: Weizhen
authors: W
authors: Zhang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D054439:Ghrelin / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D054440:Receptors, Ghrelin / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000276:immunology*; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D054439:Ghrelin; D054440:Receptors, Ghrelin; D050796:STAT3 Transcription Factor; D058570:TOR Serine-Threonine Kinases; C000592182:Ghsr protein, Mouse