滤泡调节性T细胞分化的作用机制

刘新东; 吴鑫

doi:10.16016/j.1000-5404.202010104

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滤泡调节性T细胞分化的作用机制

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- 滤泡调节性T细胞分化的作用机制
- Molecular cues govern follicular regulatory T cell differentiation
- 第三军医大学学报 2020年42卷第24期页码：2355-2357
- 作者机构：
  
  400038 重庆，陆军军医大学(第三军医大学)第一附属医院病理科，全军临床病理学研究所
- 作者简介：
  
  [ 刘新东，博士，教授，博士研究生导师。兼任Immune Network(SCI收录)编委和中华医学会病理学分会的国际交流委员等职务，是Nature，Nat Immunol，Immunity，JEM等杂志的审稿人。主持国家重点研究开发计划子课题和多项国家自然科学基金。以通信作者在Science(2020)、Nature(2014，2019)、Cell Res(2020)、J Immunol等SCI重要国际刊物上发表论著多篇，F1000收录论文多篇。主要从事T细胞分化及效应功能调控机制方面的研究。E-mail:xindongliu@hotmail.com LIU Xindong, E-mail:xindongliu@hotmail.com
- 基金信息：
  
  国家自然科学基金项目(31770973);国家自然科学基金项目(81703531)
- DOI：10.16016/j.1000-5404.202010104
  中图分类号： R392.12
- 收稿：2020-10-16，
  
  修回：2020-10-23，
  
  纸质出版：2020-12-30
- 稿件说明：
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刘新东, 吴鑫. 滤泡调节性T细胞分化的作用机制[J]. 第三军医大学学报, 2020,42(24):2355-2357.

Xindong LIU, Xin WU. Molecular cues govern follicular regulatory T cell differentiation[J]. Journal of Third Military Medical University, 2020, 42(24): 2355-2357.
刘新东, 吴鑫. 滤泡调节性T细胞分化的作用机制[J]. 第三军医大学学报, 2020,42(24):2355-2357. DOI： 10.16016/j.1000-5404.202010104.

Xindong LIU, Xin WU. Molecular cues govern follicular regulatory T cell differentiation[J]. Journal of Third Military Medical University, 2020, 42(24): 2355-2357. DOI： 10.16016/j.1000-5404.202010104.

摘要

滤泡调节性T细胞(follicular regulatory T cells

Tfr)伴随着生发中心(germinal centers

GC)反应生成，而促使Tfr细胞形成的分子线索仍然未知。本课题组研究发现硬化蛋白结构域蛋白1(sclerostin domain -containing protein 1

SOSTDC1)是Tfr细胞生成所必需的，由滤泡辅助性T细胞(follicular helper T cells

Tfh)亚群以及T-B边界区域丰富的成纤维网状基质细胞(fibroblastic reticular cells

FRCs)分泌。在动物实验(小鼠)中，运用命运示踪法和转录组学明确了表达SOSTDC1的Tfh细胞为一个独特的T细胞群，它由SOSTDC1阴性的Tfh细胞发育形成，失去了帮助B细胞产生抗体的功能。值得注意的是，Tfh细胞中SOSTDC1缺失将导致Tfr细胞数量显著减少，进而促进GC反应升高。在机制上，SOSTDC1通过阻断WNT-β-catenin信号轴，促进Tfr细胞分化。

Abstract

Follicular regulatory T (Tfr) cells are generated with the responses of germinal center (GC). However

the molecular mechanism on the cell generation is still unknown. Our study found that sclerostin domain-containing protein 1

is essential in the process of Tfr cell generation. With the aid of reporter mice

the results of fate tracking and transcriptome assessment indicated that the Tfh cells expressing SOSTDC1 are identified as a unique T cell population

are developed from SOSTDC1

Tfh cells

and have lost their ability to help B cells in the production of antibodies. It is worth noting that lack of SOSTDC1 results in substantially decreased Tfr cell numbers

and enhanced GC responses. In the aspect of mechanism

SOSTDC1 promotes the differentiation of Tfr cells by blocking Wnt-β-catenin signaling axis.

关键词

Keywords

references

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