mTOR Signaling Regulates Protective Activity of Transferred CD4+Foxp3+ T Cells in Repair of Acute Kidney Injury

T cells, with enhanced production of anti-inflammatory cytokines, which, conversely, was reduced by mTOR activation. Rapamycin, an inhibitor of mTOR, was transiently administered to C57BL/6 mice before ischemia/reperfusion surgery. No beneficial effect of rapamycin treatment was seen in the early recovery of AKI as a result of its inhibitory effect on tubular regeneration. However, rapamycin markedly enhanced the expansion of kidney Tregs, with increased mRNA expression of anti-inflammatory cytokines. Adoptive transfer of rapamycin-treated Tregs markedly suppressed conventional T cells, responder myeloid cells, and reactive myofibroblasts; however, it promoted host Tregs and alternative macrophages, leading to better renal function and less kidney fibrosis. Taken together, Treg transfer with mTOR inhibition markedly improves outcomes of ischemic AKI. These findings reveal an important role for mTOR signaling in maintaining Treg activity after adoptive transfer and highlight the therapeutic potential of targeting Tregs in acute and chronic kidney disease.