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转录因子BCL6调控先天性T细胞的早期发育
作者:小柯机器人 发布时间:2020/7/29 21:49:12

希腊基础生物医学研究所Mihalis Verykokakis、美国芝加哥大学Barbara L. Kee等研究人员合作发现,转录因子BCL6调控先天性T细胞的早期发育。相关论文于2020年7月27日在线发表在《自然—免疫学》杂志上。

研究人员发现转录因子BCL-6在从阳性选择退出后在iNKT细胞中瞬时表达,并且是其在0期以后正常发育所必需的。值得注意的是,在Bcl6不存在的情况下,MAIT细胞的发育也受到了损害。缺乏BCL-6的iNKT细胞具有与先天T细胞谱系相关基因的表达降低,包括编码PLZF的Zbtb16和靶向PLZF的基因。BCL-6促进了染色质可及性,从而允许与发育相关的基因表达,并抑制与初始T细胞程序相关的基因。
 
这些结果揭示了BCL-6的新功能,并阐明了该转录因子如何控制早期iNKT细胞的发育。
 
据介绍,先天T细胞是异质性T淋巴细胞,包括恒定自然杀伤T(iNKT)和与粘膜相关的先天T(MAIT)细胞,其效应特性在胸腺分化过程中已预先编程。目前尚不清楚如何启动该程序。
 
附:英文原文

Title: The transcription factor BCL-6 controls early development of innate-like T cells

Author: Marianthi Gioulbasani, Alexandros Galaras, Sofia Grammenoudi, Panagiotis Moulos, Alexander L. Dent, Mikael Sigvardsson, Pantelis Hatzis, Barbara L. Kee, Mihalis Verykokakis

Issue&Volume: 2020-07-27

Abstract: Innate T cells, including invariant natural killer T (iNKT) and mucosal-associated innate T (MAIT) cells, are a heterogeneous T lymphocyte population with effector properties preprogrammed during their thymic differentiation. How this program is initiated is currently unclear. Here, we show that the transcription factor BCL-6 was transiently expressed in iNKT cells upon exit from positive selection and was required for their proper development beyond stage 0. Notably, development of MAIT cells was also impaired in the absence of Bcl6. BCL-6-deficient iNKT cells had reduced expression of genes that were associated with the innate T cell lineage, including Zbtb16, which encodes PLZF, and PLZF-targeted genes. BCL-6 contributed to a chromatin accessibility landscape that was permissive for the expression of development-related genes and inhibitory for genes associated with naive T cell programs. Our results revealed new functions for BCL-6 and illuminated how this transcription factor controls early iNKT cell development.

DOI: 10.1038/s41590-020-0737-y

Source: https://www.nature.com/articles/s41590-020-0737-y

期刊信息

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:23.53
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex