分析单核细胞来源的髓样抑制细胞在心脏同种异体移植中的治疗潜力。
Analysis of therapeutic potential of monocytic myeloid-derived suppressor cells in cardiac allotransplantation.
机构信息
Atopy Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan.
Atopy Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan; Advanced Research Institute for Health Science, Juntendo University, Tokyo, Japan.
出版信息
Transpl Immunol. 2021 Aug;67:101405. doi: 10.1016/j.trim.2021.101405. Epub 2021 May 8.
BACKGROUND
Myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) are attractive immune cells to induce immune tolerance. To explore a strategy for improving the efficacy of MDSC therapies, we examined the impact of adoptive transfer of several types of MDSCs on graft rejection in a murine heart transplantation model.
METHODS
We analyzed the effects of induced syngeneic and allogeneic bone marrow-derived MDSCs (BM-MDSCs) on graft survival and suppressive capacity. We also compared the ability of syngeneic monocytic MDSCs (Mo-MDSCs) and polymorphonuclear MDSCs (PMN-MDSCs) to inhibit graft rejection and investigated the suppression mechanisms.
RESULTS
Both syngeneic and allogeneic donor- or allogeneic third-party-derived BM-MDSCs prolonged graft survival, although syngeneic BM-MDSCs inhibited anti-donor immune responses most effectively in vitro. Syngeneic Mo-MDSCs, rather than PMN-MDSCs, were responsible for immune suppression through downregulating inducible nitric oxide synthase (iNOS) and expanded naturally occurring thymic originated Treg (nTreg) in vitro. Adoptive transfer of Mo-MDSCs, but not PMN-MDSCs, prolonged graft survival and increased Treg infiltration into the graft heart.
CONCLUSION
Recipient-derived Mo-MDSCs are most effective in prolonging graft survival via inhibiting T cell response and nTreg infiltration.
背景
髓系来源的抑制细胞（MDSCs）和调节性 T 细胞（Tregs）是诱导免疫耐受的有吸引力的免疫细胞。为了探索提高 MDSC 治疗效果的策略，我们在小鼠心脏移植模型中研究了几种类型的 MDSC 过继转移对移植物排斥的影响。
方法
我们分析了诱导同基因和同种异体骨髓来源的 MDSCs（BM-MDSCs）对移植物存活和抑制能力的影响。我们还比较了同基因单核细胞来源的 MDSCs（Mo-MDSCs）和多形核 MDSCs（PMN-MDSCs）抑制移植物排斥的能力，并研究了抑制机制。
结果
同基因和异基因供体或异基因第三方来源的 BM-MDSCs 均延长了移植物存活时间，尽管同基因 BM-MDSCs 在体外最有效地抑制了抗供体免疫反应。同基因 Mo-MDSCs 而不是 PMN-MDSCs 通过下调诱导型一氧化氮合酶（iNOS）和体外扩增天然胸腺起源的调节性 T 细胞（nTreg）来发挥免疫抑制作用。Mo-MDSCs 的过继转移而不是 PMN-MDSCs 的过继转移延长了移植物存活时间，并增加了 Treg 浸润到移植物心脏。
结论
通过抑制 T 细胞反应和 nTreg 浸润，受体来源的 Mo-MDSCs 是延长移植物存活时间最有效的方法。
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