Highly inflamed and neovascularized corneal graft beds are known as high-risk (HR) environments for transplant survival. One of the primary factors leading to this rejection is reduction in the suppressive function of regulatory T cells (Treg). Our results show that myeloid-derived suppressor cells (MDSC) counteract interleukin-6–mediated Treg dysfunction by expressing interleukin-10. Additionally, MDSC maintain forkhead box P3 stability and their ability to suppress IFN-γ Th1 cells. Administering MDSC to HR corneal transplant recipients demonstrates prolonged graft survival via promotion of Treg while concurrently suppressing IFN-γ Th1 cells. Moreover, MDSC-mediated donor-specific immune tolerance leads to long-term corneal graft survival as evidenced by the higher survival rate or delayed survival of a second-party C57BL/7 (B6) graft compared to those of third-party C3H grafts observed in contralateral low-risk or HR corneal transplantation of BALB/c recipient mice, respectively. Our study provides compelling preliminary evidence demonstrating the effectiveness of MDSC in preventing Treg dysfunction, significantly improving graft survival in HR corneal transplantation, and showing promising potential for immune tolerance induction.

中文翻译：

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骨髓源性抑制细胞通过抑制高危角膜移植中的调节性 T 细胞功能障碍来促进同种异体移植物存活

高度发炎和新生血管的角膜移植床被称为移植存活的高风险（HR）环境。导致这种排斥的主要因素之一是调节性 T 细胞 (Treg) 的抑制功能降低。我们的结果表明，骨髓源性抑制细胞 (MDSC) 通过表达白细胞介素 10 来抵消白细胞介素 6 介导的 Treg 功能障碍。此外，MDSC 维持叉头盒 P3 的稳定性及其抑制 IFN-γ Th1 细胞的能力。对 HR 角膜移植受者施用 MDSC 表明，通过促进 Treg 的同时抑制 IFN-γ Th1 细胞，可以延长移植物的存活时间。此外，MDSC介导的供体特异性免疫耐受导致角膜移植物长期存活，与观察到的第三方C3H移植物相比，第二方C57BL/7 (B6)移植物的存活率更高或延迟存活就证明了这一点分别在 BALB/c 受体小鼠的对侧低风险或 HR 角膜移植中。我们的研究提供了令人信服的初步证据，证明 MDSC 在预防 Treg 功能障碍方面的有效性，显着提高 HR 角膜移植中的移植物存活率，并显示出诱导免疫耐受的良好潜力。