TCF-1 and TOX regulate the memory formation of intestinal group 2 innate lymphoid cells in asthma
Kaifan Bao, Xiaoqun Gu, Yajun Song, Yijing Zhou, Yanyan Chen, Xi Yu, Weiyuan Yuan, Liyun Shi, Jie Zheng, Min Hong
Abstract
Immune memory has been expanded to group 2 innate lymphoid cells (ILC2s), but the cellular and molecular bases remain incompletely understood. Based on house dust mite (HDM)-induced mice asthma models and human samples, we applied flow cytometry, parabiosis, in vivo imaging and adoptive transplantation to confirm the persistence, migration and function of CD45+lineage–CD90.2+NK1.1–NKp46–ST2–KLRG1+IL-17RB+ memory-like ILC2s (ml-ILC2s). Regulated by CCR9/CCL25 and S1P signaling, ml-ILC2s reside in the lamina propria of small intestines (siLP) in asthma remission, and subsequently move to airway upon re-encountering antigens or alarmins. Furthermore, ml-ILC2s possess properties of longevity, potential of rapid proliferation and producing IL-13, and display transcriptional characteristics with up-regulation of Tox and Tcf-7. ml-ILC2s transplantation restore the asthmatic changes abrogated by Tox and Tcf7 knockdown. Our data identify siLP ml-ILC2s as a memory-like subset, which promotes asthma relapse. Targeting TCF-1 and TOX might be promising for preventing asthma recurrence. TCF1 and TOX have been shown to be important in T memory cell formation. Here the authors show that TCF1 and TOX contribute to the regulation and persistence of memory-like ILC2 cells in mouse asthma models and persons with asthma.