工程化调节性T细胞调控机体免疫耐受及其生物医学应用

调节性T细胞（Tregs）是一类机体发挥免疫调节功能的T淋巴细胞亚群，能够高效、安全、可控地调节机体免疫，在自身免疫疾病及器官移植术后免疫排斥等炎症疾病的治疗应用中发挥关键作用。然而，治疗脱靶和功能表型不稳定给Tregs的临床应用带来巨大挑战。生物医学工程改造策略不仅能够促进Tregs主动靶向与炎症趋化，还可维持Tregs叉头盒蛋白p3 (Foxp3)在炎症环境中的表达稳定性，持续发挥机体免疫调节功能。本文详述Tregs的免疫调节机制，并对生物医学工程化改造的Tregs在自身免疫疾病、器官移植等炎症疾病中的应用进行展望，旨在启发和促进Tregs免疫过继疗法的临床应用研究。

Engineered Regulatory T Cells Regulate Immune Tolerance for Biomedical Applications

Regulatory T cells (Tregs) are T lymphocytes that perform immunomodulatory functions. By providing accurate, efficient, safe and controlled regulation of systemic immunity, Tregs play a key role in the treatment of autoimmune diseases and immune rejection after organ transplantation. However, Tregs have clinical limitations such as off-targeting and functional phenotype instability. Genetic and biomedical engineering are promising strategies to promote Treg active targeting and chemotaxis to the inflammation site, and to maintain Treg Forkhead box protein 3 (Foxp3) expression during immune-regulation. Herein, Treg anti-inflammatory mechanisms, engineering tactics and bulk production methods are systematically summarized. By anti-inflammatory cytokine secretion, Granzyme B release or effector T cell metabolism intervention, Tregs can inhibit effector T cell proliferation and activation, or even kill immune cells. Moreover, expressing genetically modified receptors (CARs, TCRs and CXCRs) or conjugating nanomaterials onto cell surface, can help enhance targeted recognition and maintain anti-inflammatory function of Tregs. Artificial antigen-presenting-cells or costimulatory molecules can stimulate Treg cell proliferation and activation. By prospecting the application of biomedical-engineered Tregs in autoimmune diseases, organ transplantation and other inflammatory diseases, this work aims to inspire and promote the clinical application of Tregs adoptive therapy.