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靶向辅助性T细胞17:克服移植排斥反应的新策略

Targeting T helper 17 cells: emerging strategies for overcoming transplant rejection.

作者信息

Lee Young Joon, Cho Mi-La

机构信息

Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Lab of Translational ImmunoMedicine (LaTIM), College of Medicine, The Catholic University of Korea, Seoul, Korea.

出版信息

Clin Transplant Res. 2024 Dec 31;38(4):309-325. doi: 10.4285/ctr.24.0058.

Abstract

Solid organ transplantation has significantly improved the survival rate of patients with terminal organ failure. However, its success is often compromised by allograft rejection, a process in which T helper 17 (Th17) cells play a crucial role. These cells facilitate rejection by enhancing neutrophil infiltration into the graft and by activating endothelial cells and fibroblasts. Additionally, Th17 cells can trigger the activation of other T cell types, including Th1, Th2, and CD8 T cells, further contributing to rejection. An imbalance between Th17 and regulatory T cells (Tregs) is known to promote rejection. To counteract this, immunosuppressive drugs have been developed to inhibit T cell activity and foster transplant tolerance. Another approach involves the adoptive transfer of regulatory cells, such as Tregs and myeloid-derived suppressor cells, to dampen T cell functions. This review primarily focuses on the roles of Th17 cells in rejection and their interactions with other T cell subsets. We also explore various strategies aimed at suppressing T cells to induce tolerance.

摘要

实体器官移植显著提高了终末期器官衰竭患者的生存率。然而,同种异体移植排斥反应常常会影响其成功,在这个过程中辅助性T细胞17(Th17细胞)发挥着关键作用。这些细胞通过增强中性粒细胞向移植物中的浸润以及激活内皮细胞和成纤维细胞来促进排斥反应。此外,Th17细胞可触发包括Th1、Th2和CD8 T细胞在内的其他T细胞类型的激活,进一步导致排斥反应。已知Th17细胞与调节性T细胞(Tregs)之间的失衡会促进排斥反应。为了应对这一情况,人们研发了免疫抑制药物来抑制T细胞活性并促进移植耐受。另一种方法是过继转移调节性细胞,如Tregs和髓源性抑制细胞,以抑制T细胞功能。本综述主要关注Th17细胞在排斥反应中的作用及其与其他T细胞亚群的相互作用。我们还探讨了旨在抑制T细胞以诱导耐受的各种策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f45/11732763/845f94fcd0c2/ctr-38-4-309-f1.jpg

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