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

PLoS ONE

Volumn 10, Issue 2, 2015, Pages

  Xu, Yanhui ^a   Li, Ziru ^a   Yin, Yue ^a   Lan, He ^a   Wang, Jun ^a   Zhao, Jing ^a   Feng, Juan ^a   Li, Yin ^a   Zhang, Weizhen ^a,b  

^a PEKING UNIVERSITY HEALTH SCIENCE CENTER   (China)

^b UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GHRELIN; GHRELIN RECEPTOR; LEUCINE; MAMMALIAN TARGET OF RAPAMYCIN; PEPTIDES AND PROTEINS; PROTEIN P70; STAT3 PROTEIN; TUBEROUS SCLEROSIS COMPLEX 1; UNCLASSIFIED DRUG; GHSR1A PROTEIN, MOUSE; TARGET OF RAPAMYCIN KINASE;

ADENOVIRIDAE; ANIMAL CELL; ARTICLE; CONTROLLED STUDY; IN VITRO STUDY; IN VIVO STUDY; LYMPHOCYTE DIFFERENTIATION; MALE; MOUSE; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN INTERACTION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; SPLEEN; TH17 CELL; VIRUS INFECTION; ANIMAL; C57BL MOUSE; CELL DIFFERENTIATION; CYTOLOGY; DRUG EFFECTS; GENETICS; IMMUNOLOGY; KNOCKOUT MOUSE; METABOLISM; PHOSPHORYLATION;

ADENOVIRIDAE; MAMMALIA; MUS;

ANIMALS; CELL DIFFERENTIATION; GHRELIN; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; PHOSPHORYLATION; RECEPTORS, GHRELIN; SIGNAL TRANSDUCTION; STAT3 TRANSCRIPTION FACTOR; TH17 CELLS; TOR SERINE-THREONINE KINASES;

EID: 84922575144     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0117081     Document Type: Article

References (30)

1. Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, et al. (2005) Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6: 1123-1132. PMID: 16200070
2. Yang XO, Pappu BP, Nurieva R, Akimzhanov A, Kang HS, et al. (2008) T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity 28: 29-39. doi: 10.1016/j.immuni.2007.11.016 PMID: 18164222
3. Mathur AN, Chang HC, Zisoulis DG, Stritesky GL, Yu Q, et al. (2007) Stat3 and Stat4 direct development of IL-17-secreting Th cells. J Immunol 178: 4901-4907. PMID: 17404271
4. Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ, Gurney AL (2003) Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem 278: 1910-1914. PMID: 12417590
5. Pernis AB (2009) Th17 cells in rheumatoid arthritis and systemic lupus erythematosus. J Intern Med 265: 644-652. doi: 10.1111/j.1365-2796.2009.02099.x PMID: 19493058
6. Schmechel S, Konrad A, Diegelmann J, Glas J, Wetzke M, et al. (2008) Linking genetic susceptibility to Crohn's disease with Th17 cell function: IL-22 serum levels are increased in Crohn's disease and correlate with disease activity and IL23R genotype status. Inflamm Bowel Dis 14: 204-212. PMID: 18022867
7. Dart ML, Jankowska-Gan E, Huang G, Roenneburg DA, Keller MR, et al. (2010) Interleukin-17-dependent autoimmunity to collagen type V in atherosclerosis. Circ Res 107: 1106-1116. doi: 10.1161/CIRCRESAHA.110.221069 PMID: 20814021
8. Gao Q, Jiang Y, Ma T, Zhu F, Gao F, et al. (2010) A critical function of Th17 proinflammatory cells in the development of atherosclerotic plaque in mice. J Immunol 185: 5820-5827. doi: 10.4049/jimmunol. 1000116 PMID: 20952673
9. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, et al. (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402: 656-660. PMID: 10604470
10. Gnanapavan S, Kola B, Bustin SA, Morris DG, McGee P, et al. (2002) The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab 87: 2988. PMID: 12050285
11. Hattori N (2009) Expression, regulation and biological actions of growth hormone (GH) and ghrelin in the immune system. Growth Horm IGF Res 19: 187-197. doi: 10.1016/j.ghir.2008.12.001 PMID: 19144554
12. Smith RG, Jiang H, Sun Y (2005) Developments in ghrelin biology and potential clinical relevance. Trends Endocrinol Metab 16: 436-442. PMID: 16213742
13. Theil MM, Miyake S, Mizuno M, Tomi C, Croxford JL, et al. (2009) Suppression of experimental autoimmune encephalomyelitis by ghrelin. J Immunol 183: 2859-2866. doi: 10.4049/jimmunol.0803362 PMID: 19620309
14. Gonzalez-Rey E, Chorny A, Delgado M (2006) Therapeutic action of ghrelin in a mouse model of colitis. Gastroenterology 130: 1707-1720. PMID: 16697735
15. Xia Q, Pang W, Pan H, Zheng Y, Kang JS, et al. (2004) Effects of ghrelin on the proliferation and secretion of splenic T lymphocytes in mice. Regul Pept 122: 173-178. PMID: 15491788
16. Dixit VD, Schaffer EM, Pyle RS, Collins GD, Sakthivel SK, et al. (2004) Ghrelin inhibits leptin-and activation-induced proinflammatory cytokine expression by human monocytes and T cells. J Clin Invest 114: 57-66. PMID: 15232612
17. Dixit VD, Yang H, Cooper-Jenkins A, Giri BB, Patel K, et al. (2009) Reduction of T cell-derived ghrelin enhances proinflammatory cytokine expression: Implications for age-associated increases in inflammation. Blood 113: 5202-5205. doi: 10.1182/blood-2008-09-181255 PMID: 19324904
18. Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, et al. (2006) The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126: 1121-1133. PMID: 16990136
19. Xu X, Ye L, Araki K, Ahmed R (2012) mTOR, linking metabolism and immunity. Semin Immunol 24: 429-435. doi: 10.1016/j.smim.2012.12.005 PMID: 23352227
20. Delgoffe GM, Powell JD (2009) mTOR: Taking cues from the immune microenvironment. Immunology 127: 459-465. doi: 10.1111/j.1365-2567.2009.03125.x PMID: 19604300
21. Kopf H, de la Rosa GM, Howard OM, Chen X (2007) Rapamycin inhibits differentiation of Th17 cells and promotes generation of FoxP3+ T regulatory cells. Int Immunopharmacol 7: 1819-1824. PMID: 17996694
22. Zhou Z, Sun W, Liang Y, Gao Y, Kong W, et al. (2012) Fenofibrate inhibited the differentiation of T helper 17 cells in vitro. PPAR Res 2012: 145654. doi: 10.1155/2012/145654 PMID: 22792085
23. Zhou L, Lopes JE, Chong MM, Ivanov II, Min R, et al. (2008) TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function. Nature 453: 236-240. doi: 10.1038/nature06878 PMID: 18368049
24. Li Z, Li Y, ZhangW(2013) Ghrelin receptor in energy homeostasis and obesity pathogenesis. Prog Mol Biol Transl Sci 114: 45-87. doi: 10.1016/B978-0-12-386933-3.00002-9 PMID: 23317782
25. Zhang H, Cui Z, Luo G, Zhang J, Ma T, et al. (2013) Ghrelin attenuates intestinal ischemia/reperfusion injury in mice by activating the mTOR signaling pathway. Int J Mol Med 32: 851-859. doi: 10.3892/ijmm.2013.1452 PMID: 23877278
26. Zhang W, Zhang C, Fritze D, Chai B, Li J, et al. (2013) Modulation of food intake by mTOR signalling in the dorsal motor nucleus of the vagus in male rats: Focus on ghrelin and nesfatin-1. Exp Physiol 98: 1696-1704. doi: 10.1113/expphysiol.2013.074930 PMID: 23955309
27. Zhu J, Zheng C, Chen J, Luo J, Su B, et al. (2014) Ghrelin protects human umbilical vein endothelial cells against high glucose-induced apoptosis via mTOR/P70S6K signaling pathway. Peptides 52: 23-28. doi: 10.1016/j.peptides.2013.11.015 PMID: 24287118
28. Durant L, Watford WT, Ramos HL, Laurence A, Vahedi G, et al. (2010) Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis. Immunity 32: 605-615. doi: 10. 1016/j.immuni.2010.05.003 PMID: 20493732
29. Souza-Moreira L, Delgado-Maroto V, Morell M, O'Valle F, Del Moral RG, et al. (2013) Therapeutic effect of ghrelin in experimental autoimmune encephalomyelitis by inhibiting antigen-specific Th1/Th17 responses and inducing regulatory T cells. Brain Behav Immun 30: 54-60. doi: 10.1016/j.bbi.2013.01. 080 PMID: 23376169
30. Zhou J, Wulfkuhle J, Zhang H, Gu P, Yang Y, et al. (2007) Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proc Natl Acad Sci U S A 104: 16158-16163. PMID: 17911267