mTOR Signaling pathway as a master regulator of memory CD8⁺ T‐cells, Th17, and NK cells development and their functional properties

Abstract

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.

Sex and Gender Aspects for Patient Stratification in Allergy Prevention and Treatment

“…The kinase mTOR intervene in T helper growth, proliferation, and metabolism. Th1, Th2, and Th17 differentiation depends on mTOR activity while its inhibition favors Treg differentiation [39,40]. mTORc1 activation is required for differentiation towards all effectors lineages including Th2, since its inhibition through RAPTOR deletion powerfully interrupt the process and induces Th17 differentiation [41,42].…”

Master regulator genes and their impact on major diseases

“…The novel concern for mTOR is also because it is a master regulator of the inflammatory response in immune and non-immune cells and implicated in a number of chronic inflammatory diseases, especially rheumatic diseases, such as systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, sjogren syndrome and seronegative spondyloarthropathy (Suto & Karonitsch, 2020). mTOR signaling pathway acts as a master regulator in memory CD8 + T − cells, Th17, and NK cells development and their functional properties (Rostamzadeh et al, 2019). Researchers used RNAi system to specifically knockdown mTOR, raptor, S6K1, eIF4E, and FKBP12 expressions in antigenmune CD8 + T − cells and the results have demonstrated that mTOR acts as the key regulator of memory CD8 + T − cells differentiation.…”

IL-17A as a Potential Therapeutic Target for Patients on Peritoneal Dialysis

“…The mammalian target of rapamycin (mTOR) signaling pathway plays a key role in Th17/Treg differentiation as well as in CD8 + T cell and NK cell proliferation and maturation [ 252 ]. mTOR activation under hypoxic conditions accelerates Th17 differentiation of naive CD4 + T cells via induction of hypoxia-induced factor-1 (HIF-1) and RORγt activation with subsequent induction of IL-17A and IL-23 production [ 253 ].…”