JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)

Proapoptotic protein Bim regulates the suppressive function of Treg cells

Author(s): Di WU
Affiliation(s): Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China
Corresponding email(s): diwu@zju.edu.cn
Key Words: Regulatory T cells; Bim; Tumor immune therapy; Senescence of immune system

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Di WU. Proapoptotic protein Bim regulates the suppressive function of Treg cells[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2300288

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Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: Regulatory T (Treg) cells are a special immunosuppressive subset of cluster of differentiation 4-positive (CD4^+‍)‍-T lymphocytes and play a pivotal role in the establishment of immune homeostasis in vivo (Zhang et al., 2021). The transcription factor forkhead box protein P3 (Foxp3) is the master marker of Treg cells, which is highly expressed in Treg cells and is also essential for their suppressive function (Hori et al., 2003). In addition to Foxp3, other regulators of Treg cells have been discovered (Wu et al., 2017, 2022; Wu and Sun, 2023a, 2023b); however, a deeper understanding of the regulation of these cells is required.

促凋亡蛋白质Bim调控Treg细胞的免疫抑制功能

吴迪
浙江大学医学院附属第二医院肿瘤研究所（恶性肿瘤预警与干预教育部重点实验室），中国杭州市，310009
摘要：调节性T细胞（Treg细胞）是一种特殊的免疫抑制性CD4⁺-T淋巴细胞亚群，具有维持机体免疫稳态的重要作用。有研究证实，促凋亡蛋白Bim参与Treg细胞功能的调控，但是还没有使用条件性敲除小鼠对Bim在Treg细胞中功能研究的报道，且Treg细胞中Bim发挥功能的机制也不清楚。已知Bim在衰老的Treg细胞中丰度下调，然而该过程在Treg细胞衰老过程中的具体作用尚不清楚。本研究中，作者繁育产生Foxp3^Cre;Bim^fl/fl条件性敲除小鼠，特异性在Treg细胞中敲除Bim。Foxp3^Cre;Bim^fl/fl小鼠可育，但是出现多器官炎性细胞浸润和免疫细胞的过度激活，这表明Bim可以调节Treg细胞免疫抑制功能。Bim缺失导致Treg细胞转录组变化，以及Ctla4基因和多个信号通路的下调。Treg细胞中Bim的缺失可以抑制胆管癌的增殖，并延长胆管癌小鼠的生存期。Bim缺失的Treg细胞，不能复现衰老Treg细胞的转录组变化，这表明Bim的下调可能是Treg细胞衰老过程中的下游事件。

关键词组：调节性T细胞；Bim；肿瘤免疫治疗；免疫系统衰老

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Reference

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促凋亡蛋白质Bim调控Treg细胞的免疫抑制功能

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