title: mTOR regulates neuroprotective effect of immunized CD4+Foxp3+ T cells in optic nerve ischemia.
abstract: 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.
authors.affiliation: Department of Nephrology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China.
authors.forename: Guochun
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China.
authors.forename: Luosheng
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Ophthalmology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Ophthalmology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China.
authors.forename: Yunping
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China.
authors.forename: Xuanchu
authors.initials: X
authors.lastname: Duan
authors.affiliation: Department of Ophthalmology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000276:immunology*; D007108:Immune Tolerance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018917:Optic Neuropathy, Ischemic / Q000517:prevention & control*; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*
chemical_list: D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases