Journal
JOURNAL OF CELLULAR PHYSIOLOGY
Volume 234, Issue 8, Pages 12353-12368Publisher
WILEY
DOI: 10.1002/jcp.28042
Keywords
immune responses; memory CD8(+) T-cell; mTOR; NK cell; regulatory T-cell; Th17
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Funding
- Drug Applied Research Center, Tabriz University of Medical Sciences
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The mammalian target of rapamycin (mTOR) is a member of the evolutionary phosphatidylinositol kinase-related kinases (PIKKs). mTOR plays a pivotal role in the regulation of diverse aspects of cellular physiology such as body metabolism, cell growth, protein synthesis, cell size, autophagy, and cell differentiation. Immunologically, mTOR has a fundamental part in controlling and shaping diverse functions of innate and adaptive immune cells, in particular, T-cell subsets differentiation, survival, and metabolic reprogramming to ultimately regulate the fate of diverse immune cell types. Researchers report that rapamycin, a selective mTOR inhibitor, and immunosuppressive agent, has surprising immunostimulatory effects on inducing both quantitative and qualitative aspects of virus-specific memory CD8(+) T-cells differentiation and homeostasis in a T-cell-intrinsic manner. The mTOR signaling pathway also plays a critical role in dictating the outcome of regulatory T cells (Treg), T helper 17 (Th17) cells, and natural killer (NK) cells proliferation and maturation, as well as the effector functions and cytotoxic properties of NK cells. Manipulation of mTOR activity is a critical therapeutic approach for pharmacological agents that seek to inhibit mTOR. This approach should enhance specific memory CD8 (+) T-cells responses and induce fully functional effector properties of NK cells to provoke their antitumor and antiviral activities.
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