title: mTORC1 signaling and IL-17 expression: Defining pathways and possible therapeutic targets.
abstract: IL-17 mediates immune responses against extracellular pathogens, and it is associated with the development and pathogenesis of various autoimmune diseases. The expression of IL-17 is regulated by various intracellular signaling cascades. Recently, it has been shown that mechanistic target of rapamycin (mTOR) signaling, comprised mainly of mTORC1 signaling, plays a critical role in IL-17 expression. Here, we review the current knowledge regarding mechanisms by which mTORC1 regulates IL-17 expression. mTORC1 positively modulates IL-17 expression through several pathways, i.e. STAT3, -HIF-1α, -S6K1, and -S6K2. Amino acids (AAs) also regulate IL-17 expression by being the energy source for Th17 cells, and by activating mTORC1 signaling. Altogether, the AA-mTORC1-IL-17 axis has broad therapeutic implications for IL-17-associated diseases, such as EAE, allergies, and colitis.
authors.affiliation: Laboratory of Animal Nutrition and Health and Key Laboratory of Agro-Ecology, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, Hunan, P. R. China.|University of the Chinese Academy of Sciences, Beijing, China.
authors.forename: Wenkai
authors.initials: W
authors.lastname: Ren
authors.affiliation: Laboratory of Animal Nutrition and Health and Key Laboratory of Agro-Ecology, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, Hunan, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yin
authors.affiliation: Laboratory of Animal Nutrition and Health and Key Laboratory of Agro-Ecology, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, Hunan, P. R. China.
authors.forename: Jielin
authors.initials: J
authors.lastname: Duan
authors.affiliation: Laboratory of Animal Nutrition and Health and Key Laboratory of Agro-Ecology, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, Hunan, P. R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Laboratory of Animal Nutrition and Health and Key Laboratory of Agro-Ecology, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, Hunan, P. R. China.
authors.forename: Bie
authors.initials: B
authors.lastname: Tan
authors.affiliation: Department of Animal Science, University of Florida, Gainesville, FL, USA.
authors.forename: Guan
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Animal Science, Texas A&M University, TAMU, TX, USA.
authors.forename: Guoyao
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Animal Science, Texas A&M University, TAMU, TX, USA.
authors.forename: Fuller W
authors.initials: FW
authors.lastname: Bazer
authors.affiliation: Chongqing Key Laboratory of Forage and Herbivorce, College of Animal Science and Technology, Southwest University, Chongqing, China.
authors.forename: Yuanyi
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Laboratory of Animal Nutrition and Health and Key Laboratory of Agro-Ecology, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, Hunan, P. R. China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Yin
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000628:therapy; D005786:Gene Expression Regulation; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000628:therapy; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D058990:Molecular Targeted Therapy; D046912:Multiprotein Complexes / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D020381:Interleukin-17; D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases
keywords: Amino acid ⋅ IL-17 ⋅ mTORC1 ⋅ STAT ⋅ HIF-1α