Immunosuppressive potency of mechanistic target of rapamycin inhibitors in solid-organ transplantati

来源 :World Journal of Transplantation | 被引量 : 0次 | 上传用户:wangyuange
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Mammalian target of rapamycin, also known as me-chanistic target of rapamycin(m TOR) is a protein kinase that belongs to the PI3K/AKT/m TOR signaling pathway, which is involved in several fundamental cellular functions such as cell growth, proliferation, and survival. This protein and its associated pathway have been implicated in cancer development and the regulation of immune responses, including the rejection response generated following allograft transplantation. Inhibitors of m TOR(m TORi) such as rapamycin and its derivative everolimus are potent immunosuppressive drugs that both maintain similar rates of efficacy and could optimize the renal function and diminish the side effects compared with calcineurin inhibitors. These drugs are used in solid-organ transplantationtoinduceimmunosuppression while also promoting the expansion of CD4+CD25+FOXP3+ regulatory T-cells that could favor a scenery of immu-nological tolerance. In this review, we describe the mechanisms by which inhibitors of m TOR induce sup-pression by regulation of these pathways at different levels of the immune response. In addition, we par-ticularly emphasize about the main methods that are used to assess the potency of immunosuppressive drugs, highlighting the studies carried out about immunosuppressive potency of inhibitors of m TOR. Mammalian target of rapamycin, also known as me-chanistic target of rapamycin (m TOR) is a protein kinase that belongs to the PI3K / AKT / m TOR signaling pathway, which is involved in several fundamental cellular functions such as cell growth, proliferation, Inhibitors of m TOR (m TORi) such as rapamycin and its derivative of everolimus are potent immunosuppressive drugs that both maintain similar rates of efficacy and could optimize the renal function and diminish the side effects compared with calcineurin inhibitors. These drugs are used in solid-organ transplantationtoinduceimmunosuppression while also promoting the expansion of CD4 + CD25 + FOXP3 + regulatory T-cells that could favor a scenery of immu-nological tolerance. In this review, we describe the mechanisms by which inhibito rs of m TOR inducers sup-pression by regulation of these pathways at different levels of the immune response. In addition, we evaluate the potency of immunosuppressive drugs, highlighting the studies carried out about immunosuppressive potency of inhibitors of m TOR.
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