Ex Vivo-Induced Bone Marrow-Derived Myeloid Suppressor Cells Prevent Corneal Allograft Rejection in Mice.
Ex Vivo-Induced Bone Marrow-Derived Myeloid Suppressor Cells Prevent Corneal Allograft Rejection in Mice.
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DOI：
10.1167/iovs.62.7.3
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发表时间：
2021-06-01
影响因子：
4.4
通讯作者：
Murakami A
中科院分区：
文献类型：
--
作者：
Zhu J;Inomata T;Fujimoto K;Uchida K;Fujio K;Nagino K;Miura M;Negishi N;Okumura Y;Akasaki Y;Hirosawa K;Kuwahara M;Eguchi A;Shokirova H;Yanagawa A;Midorikawa-Inomata A;Murakami A
目的探讨体外诱导骨髓源性抑制细胞(BM-MDSCs)对角膜移植异基因免疫反应的影响。C57BL/6J(B6)小鼠骨髓细胞与IL-6和GM-CSF共同培养4d。采用流式细胞术、逆转录-定量聚合酶链式反应检测诱导型一氧化氮合酶(INOS)mRNA的表达以及同种异体刺激下一氧化氮(NO)的产生来评价BM-MDSCs的体外诱导。在体外诱导的BM-MDSCs存在下，研究同种异体刺激下T细胞的增殖和调节性T细胞(Treg)的扩增。采用酶联免疫吸附试验检测干扰素-γ、IL-2、IL-10和转化生长因子-β1蛋白水平。在结膜下注射体外诱导的BM-MDSCs后，用流式细胞仪、裂隙灯显微镜和免疫组织化学检测BM-MDSCs向角膜移植物的迁移、同种异体角膜移植物的存活率、新生血管和淋巴管的生成。联合应用GM-CSF和IL-6可显著诱导BM-MDSCs，并增加inos基因的表达。体外诱导的BM-MDSCs在同种异体刺激下可促进NO的释放。体外诱导的BM-MDSCs抑制T细胞增殖，促进Treg增殖。体外诱导的骨髓间充质干细胞共培养后，干扰素-γ减少，IL-2、IL-10和转化生长因子-β-1的产生增加。注射体外诱导的BM-MDSCs被证实能迁移到移植物中。注射的BM-MDSCs还延长了角膜移植物的存活时间，并阻止了血管生成和淋巴管生成。体外诱导的BM-MDSCs通过iNOS途径抑制同种异体免疫反应，延长同种异体角膜移植物存活时间，有望成为角膜移植的潜在治疗手段。
To investigate the effects of ex vivo–induced bone marrow myeloid-derived suppressor cells (BM-MDSCs) on allogeneic immune responses in corneal transplantation. Bone marrow cells from C57BL/6J (B6) mice were cultured with IL-6 and GM-CSF for four days. The ex vivo induction of the BM-MDSCs was assessed using flow cytometry, inducible nitric oxide synthase (iNOS) mRNA expression using reverse transcription–quantitative polymerase chain reaction, and nitric oxide (NO) production in allogeneic stimulation. T-cell proliferation and regulatory T-cell (Treg) expansion were investigated on allogeneic stimulation in the presence of ex vivo–induced BM-MDSCs. IFN-γ, IL-2, IL-10, and TGF-β1 protein levels were measured using enzyme-linked immunosorbent assays. After subconjunctival injection of ex vivo–induced BM-MDSCs, the migration of the BM-MDSCs into corneal grafts, allogeneic corneal graft survival, neovascularization, and lymphangiogenesis were assessed using flow cytometry, slit-lamp microscopy, and immunohistochemistry. The combination of GM-CSF and IL-6 significantly induced BM-MDSCs with increased iNos mRNA expression. The ex vivo–induced BM-MDSCs promoted NO release in allogeneic stimulation in vitro. The ex vivo–induced BM-MDSCs inhibited T-cell proliferation and promoted Treg expansion. Decreased IFN-γ and increased IL-2, IL-10, and TGF-β1 production was observed in coculture of ex vivo–induced BM-MDSCs. Injected ex vivo–induced BM-MDSCs were confirmed to migrate into the grafts. The injected BM-MDSCs also prolonged corneal graft survival and prevented angiogenesis and lymphangiogenesis. The ex vivo–induced BM-MDSCs have suppressive effects on allogeneic immune responses and prolong corneal allograft survival via the iNOS pathway, indicating that they may be a potential therapeutic tool for corneal transplantation.
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影响因子：
10.1
作者：
Gabrilovich DI
通讯作者：
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影响因子：
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作者：
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