mTORC1 signaling and IL-17 expression: Defining pathways and possible therapeutic targets.
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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-1, -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.
author list (cited authors)
Ren, W., Yin, J., Duan, J., Liu, G., Tan, B., Yang, G., ... Yin, Y.
complete list of authors
Ren, Wenkai||Yin, Jie||Duan, Jielin||Liu, Gang||Tan, Bie||Yang, Guan||Wu, Guoyao||Bazer, Fuller W||Peng, Yuanyi||Yin, Yulong