mTOR regulates neuroprotective effect of immunized CD4+Foxp3+ T cells in optic nerve ischemia.
mTOR regulates neuroprotective effect of immunized CD4+Foxp3+ T cells in optic nerve ischemia.
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mTOR 调节免疫 CD4 Foxp3 T 细胞在视神经缺血中的神经保护作用
DOI：
10.1038/srep37805
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发表时间：
2016-11-25
影响因子：
4.6
通讯作者：
Chen H
中科院分区：
文献类型：
--
作者：
Chen G;Tang L;Wei W;Li Z;Li Y;Duan X;Chen H
靶向CD 4 + Foxp 3+调节性T细胞（Tcells）在神经炎症条件下的治疗潜力仍然存在争议。本研究旨在探讨TdR在视神经缺血（ONI）中的神经保护作用，并评估TdR转移的治疗策略，重点是靶向哺乳动物雷帕霉素靶蛋白（mTOR）通路。在成年C57 BL/6小鼠中瞬时增加眼内压以诱导ONI。髓磷脂碱性蛋白（MBP）的粘液耐受通过增强Tcl 3抑制显著增加ONI后视网膜神经节细胞（RGC）的存活。mTOR抑制显著促进体外MBP免疫的TCRs的频率，并增加抗炎细胞因子的产生。瞬时雷帕霉素治疗高度促进TdR的免疫抑制能力，并抑制ONI动物的视网膜炎症。静脉内输注MBP免疫的TGFAP，而不是常规的TGFAP，有益地调节宿主视网膜CD 11b+细胞和CD 4+效应T细胞的免疫活性，导致RGC存活的显著改善。重要的是，雷帕霉素治疗进一步增强了TGFAP转移的神经保护作用。综上所述，这些发现揭示了急性视网膜损伤后mTOR信号转导对免疫TdR的精细调节。靶向mTOR策略的连续转移显著改善了ONI后的神经元恢复，支持TdR在急性和慢性神经系统疾病中的治疗潜力。
The therapeutic potential of targeting CD4+Foxp3+ regulatory T cells (Tregs) remains controversial under the condition of neuroinflammation. This study aims to explore the neuroprotective role of Tregs in optic nerve ischemia (ONI) and evaluate the therapeutic strategy of Tregs transfer with a focus on targeting the mammalian target of rapamycin (mTOR) pathway. Intraocular pressure was transiently increased in adult C57BL/6 mice to induce ONI. Mucosal tolerance of myelin basic protein (MBP) markedly increased retinal ganglion cell (RGC) survival after ONI through enhanced Tregs suppression. mTOR inhibition significantly promoted the frequency of MBP-immunized Tregs in vitro with increased production of anti-inflammatory cytokines. Transient rapamycin treatment highly promoted the immunosuppressive capacity of Tregs and inhibited retinal inflammation in ONI animals. Intravenous infusion of MBP-immunized Tregs, instead of regular Tregs, beneficially modulated immune activities of host retinal CD11b+ cells and CD4+ effector T cells, leading to significant improvement of RGC survival. Importantly, rapamycin treatment further enhanced the neuroprotective effect of Tregs transfer. Taken together, these findings reveal a fine regulation of mTOR signaling on immunized Tregs after acute retinal injury. Adoptive transfer with targeting-mTOR strategy markedly improves neuronal recovery after ONI, supporting the therapeutic potentials of Tregs in acute and chronic neurological disorder.
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影响因子：
4.4
作者：
Burchill, Matthew A.;Yang, Jianying;Farrar, Michael A.
通讯作者：
Farrar, Michael A.
影响因子：
82.9
作者：
Liesz, Arthur;Suri-Payer, Elisabeth;Veltkamp, Roland
通讯作者：
Veltkamp, Roland
影响因子：
4.1
作者：
Ayer RE;Jafarian N;Chen W;Applegate RL 2nd;Colohan AR;Zhang JH
通讯作者：
Zhang JH
DOI：
10.1038/nri3198
发表时间：
2012-04-20
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
15.9
作者：
Hoeffer, Charles A.;Klann, Eric
通讯作者：
Klann, Eric