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Wnt–β-catenin激活可在炎症性肠病中对Treg细胞进行表观重塑
作者:小柯机器人 发布时间:2021/3/7 22:16:35

美国芝加哥大学Fotini Gounari、梅奥临床医学院Khashayarsha Khazaie等研究人员合作发现,Wnt–β-catenin激活可在炎症性肠病中对Treg细胞进行表观重塑。2021年3月4日,《自然—免疫学》杂志在线发表了这项成果。

研究人员发现,在炎症和早期不典型增生的炎症性肠病患者中,RORγt+ 调节性T(Treg)细胞存在逐渐扩增。激活人和鼠Treg细胞中的Wnt-β-catenin信号足以重现疾病相关RORγt+ Treg细胞频率的增加,这些细胞共表达多种促炎性细胞因子。β-catenin相互作用伴侣TCF-1与DNA的结合跟促炎途径基因中Foxp3结合的增强子位点存在重叠。持续的Wnt-β-catenin活化会诱导这些基因中新的可及性染色质位点,并上调其表达。

这些发现表明,TCF-1和Foxp3一起限制了Treg细胞中促炎基因的表达。β-catenin信号的激活会干扰该功能,并促进与疾病相关的RORγt+ Treg表型。 

据悉,目前尚不清楚健康和疾病中Treg细胞的多样性。结直肠癌患者具有RORγt+ Treg细胞亚群,其β-catenin表达升高且具有促炎特性。

附:英文原文

Title: Wnt–β-catenin activation epigenetically reprograms T reg cells in inflammatory bowel disease and dysplastic progression

Author: Jasmin Quandt, Stephen Arnovitz, Leila Haghi, Janine Woehlk, Azam Mohsin, Michael Okoreeh, Priya S. Mathur, Akinola Olumide Emmanuel, Abu Osman, Manisha Krishnan, Samuel B. Morin, Alexander T. Pearson, Randy F. Sweis, Joel Pekow, Christopher R. Weber, Khashayarsha Khazaie, Fotini Gounari

Issue&Volume: 2021-03-04

Abstract: The diversity of regulatory T (Treg) cells in health and in disease remains unclear. Individuals with colorectal cancer harbor a subpopulation of RORγt+ Treg cells with elevated expression of β-catenin and pro-inflammatory properties. Here we show progressive expansion of RORγt+ Treg cells in individuals with inflammatory bowel disease during inflammation and early dysplasia. Activating Wnt–β-catenin signaling in human and murine Treg cells was sufficient to recapitulate the disease-associated increase in the frequency of RORγt+ Treg cells coexpressing multiple pro-inflammatory cytokines. Binding of the β-catenin interacting partner, TCF-1, to DNA overlapped with Foxp3 binding at enhancer sites of pro-inflammatory pathway genes. Sustained Wnt–β-catenin activation induced newly accessible chromatin sites in these genes and upregulated their expression. These findings indicate that TCF-1 and Foxp3 together limit the expression of pro-inflammatory genes in Treg cells. Activation of β-catenin signaling interferes with this function and promotes the disease-associated RORγt+ Treg phenotype.

DOI: 10.1038/s41590-021-00889-2

Source: https://www.nature.com/articles/s41590-021-00889-2

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