美国哥伦比亚大学Sankar Ghosh课题组的一项最新研究研制了预先存在的表观遗传状态和差异NF-κB激活形成2型免疫细胞反应。该项研究成果发表在2025年5月13日出版的《免疫学》上。

小组研究了2型免疫的转录调控，聚焦于NF-κB通路，该通路被TCR参与或细胞因子信号传导不同地激活。NF-κB亚单位c-Rel和p65的条件缺失限制了ILC2s中关键2型基因（包括Il13和Il5）的表达，而在Th2细胞中则没有。全基因组分析显示，这些基因的调控区域在ILC2s中以开放的染色质状态存在，允许NF-κB在IL-33刺激下结合。这些区域在未受刺激的Th2细胞中不易接近，在那里NFAT起主导作用。因此，p65缺失会在气道炎症和蠕虫感染期间破坏ILC2的激活和功能。先天淋巴细胞和适应性淋巴细胞利用不同的表观遗传景观和转录调节因子来控制共享的效应基因。

据了解，CD4⁺ T辅助2 （Th2）细胞和2组先天淋巴样细胞（ILC2s）通过相似的效应分子驱动2型免疫反应，这些效应分子主要由不同的信号诱导- IL -33在ILC2s和TCR参与Th2细胞。

附：英文原文

Title: Pre-existing epigenetic state and differential NF-κB activation shape type 2 immune cell responses

Author: Vincent Guichard, Felipe Batista Leo, Jingyao Zhao, Yingyu Zhang, Takamasa Ito, Simon Shirley, Thomas S. Postler, Ruxiao Tian, Yuefeng Huang, Sankar Ghosh

Issue&Volume: 2025-05-13

Abstract: CD4+ T helper 2 (Th2) cells and group 2 innate lymphoid cells (ILC2s) drive type 2 immune responses via similar effector molecules that are primarily induced by different signals—interleukin (IL)-33 in ILC2s and TCR engagement in Th2 cells. Here, we examined the transcriptional regulation of type 2 immunity, focusing on the NF-κB pathway, which is differentially activated by TCR engagement or cytokine signaling. Conditional deletion of the NF-κB subunits c-Rel and p65 limited the expression of key type 2 genes, including Il13 and Il5, in ILC2s but not in Th2 cells. Genome-wide analysis revealed that the regulatory regions of such genes exist in an open chromatin state in ILC2s, allowing NF-κB binding upon IL-33 stimulation. These regions are less accessible in unstimulated Th2 cells, where NFAT plays a dominant role. Accordingly, p65 deletion impaired ILC2 activation and function during airway inflammation and helminth infection. Thus, innate and adaptive lymphocytes leverage distinct epigenetic landscapes and transcriptional regulators to control shared effector genes.

DOI: 10.1016/j.immuni.2025.04.016

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00179-7