Tissue signals imprint Aiolos expression in ILC2s to modulate type 2 immunity
Jinxin Qiu, Jingjing Zhang, Yanhui Ma, Hanxiao Sun, Zhitao Gu, Qiangling Sun, Meizhu Bai, Jue Gong, Jupei Tang, Yunpeng Zhang, Shiyang Li, Zhen Shao, Jinsong Li, Huiming Sheng, Lei Shen, Ju Qiu
Abstract
ILC2s through inhibiting PD-1. At the epigenetic level, ILC2 tissue characters are imprinted by open chromatin regions (OCRs) at non-promoters. Intestinal-specific transcription factor aryl hydrocarbon receptor (Ahr) binds to Ikzf3 (encoding Aiolos) locus, increases the accessibility of an intestinal ILC2-specific OCR, and promotes the Ikzf3 transcription by enhancing H3K27ac. Consequently, Ahr prevents ILC2s entering an "exhausted-like" state through sustaining Aiolos expression. Our work elucidates mechanism of ILC2 tissue adaptation and highlights Aiolos as a potential target of type 2 inflammation.