小柯机器人

美国拉霍亚过敏和免疫学研究所Shane Crotty研究组的最新研究，探明了Bcl-6是阻遏物回路诱导T卵泡辅助细胞（T_FH）的联系转录因子。这一研究成果于2020年6月22日发表在《自然-免疫学》上。

T_FH是一种独特的CD4 ⁺ T细胞类型，对于大多数抗体和B淋巴细胞反应都是必不可少的。T_FH细胞的正常和异常调控与多种疾病有关。Bcl-6是通过谱系确定的T_FH细胞转录因子，其活性对于T_FH细胞的分化和功能至关重要。

但是，Bcl-6如何调控T_FH的生物学基础仍然不清楚。这部分是由于在具有多种可能分化命运的复杂细胞类型中，阻遏物与基因上调之间的内在挑战造成的。

研究人员通过一系列实验方法测试了多个竞争模型，以确定Bcl-6如何表现出负自动调节功能，并通过多个阻遏物基因回路控制T_FH分化和功能的多效性属性，包括迁移、共刺激、抑制性受体和细胞因子。

附：英文原文

Title: Bcl-6 is the nexus transcription factor of T follicular helper cells via repressor-of-repressor circuits

Author: Jinyong Choi, Huitian Diao, Caterina E. Faliti, Jacquelyn Truong, Meghan Rossi, Simon Blanger, Bingfei Yu, Ananda W. Goldrath, Matthew E. Pipkin, Shane Crotty

Issue&Volume: 2020-06-22

Abstract: T follicular helper (TFH) cells are a distinct type of CD4+ T cells that are essential for most antibody and B lymphocyte responses. TFH cell regulation and dysregulation is involved in a range of diseases. Bcl-6 is the lineage-defining transcription factor of TFH cells and its activity is essential for TFH cell differentiation and function. However, how Bcl-6 controls TFH biology has largely remained unclear, at least in part due to the intrinsic challenges of connecting repressors to gene upregulation in complex cell types with multiple possible differentiation fates. Multiple competing models were tested here by a series of experimental approaches to determine that Bcl-6 exhibits negative autoregulation and controls pleiotropic attributes of TFH differentiation and function, including migration, costimulation, inhibitory receptors and cytokines, via multiple repressor-of-repressor gene circuits. Bcl-6 is the signature transcription factor for TFH cells. Crotty and colleagues provide a comprehensive transcriptional map depicting the regulatory circuitry controlled by Bcl-6 in determining TFH cell fate and function.

DOI: 10.1038/s41590-020-0706-5

Source: https://www.nature.com/articles/s41590-020-0706-5

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：31.25
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