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肝脏微环境中的调节性T细胞代谢

Regulatory T Cell Metabolism in the Hepatic Microenvironment.

作者信息

Wawman Rebecca Ellen, Bartlett Helen, Oo Ye Htun

机构信息

Centre for Liver Research, National Institute of Health Research Birmingham Biomedical Research Centre, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.

Faculty of Health and Life Sciences, School of Life Sciences, Coventry University, Coventry, United Kingdom.

出版信息

Front Immunol. 2018 Jan 8;8:1889. doi: 10.3389/fimmu.2017.01889. eCollection 2017.

Abstract

Thymic-derived naturally occurring regulatory T cells (tTreg) are crucial for maintaining peripheral immune homeostasis. They play a crucial role in preventing autoimmunity and maintaining organ transplant without requiring immunosuppression. Cellular metabolism has recently emerged as an important regulator of adaptive immune cell balance between Treg and effector T cells. While the metabolic requirements of conventional T cells are increasingly understood, the role of Treg cellular metabolism is less clear. The continuous exposure of metabolites and nutrients to the human liver the portal blood flow influences the lineage fitness, function, proliferation, migration, and survival of Treg cells. As cellular metabolism has an impact on its function, it is crucial to understand the metabolic pathways wiring in regulatory T cells. Currently, there are ongoing early phase clinical trials with polyclonal and antigen-specific good manufacturing practice (GMP) Treg therapy to treat autoimmune diseases and organ transplantation. Thus, enhancing immunometabolic pathways of Treg by translational approach with existing or new drugs would utilize Treg cells to their full potential for effective cellular therapy.

摘要

胸腺来源的天然调节性T细胞(tTreg)对于维持外周免疫稳态至关重要。它们在预防自身免疫和维持器官移植而无需免疫抑制方面发挥着关键作用。细胞代谢最近已成为调节Treg和效应T细胞之间适应性免疫细胞平衡的重要因素。虽然传统T细胞的代谢需求越来越为人所知,但Treg细胞代谢的作用尚不清楚。代谢物和营养物质通过门静脉血流持续暴露于人体肝脏,这会影响Treg细胞的谱系适应性、功能、增殖、迁移和存活。由于细胞代谢会影响其功能,了解调节性T细胞中的代谢途径至关重要。目前,正在进行多项早期临床试验,采用多克隆和抗原特异性的药品生产质量管理规范(GMP)Treg疗法来治疗自身免疫性疾病和器官移植。因此,通过使用现有或新药的转化方法增强Treg的免疫代谢途径,将充分发挥Treg细胞的潜力,实现有效的细胞治疗。

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