TCF-1 and TOX regulate the memory formation of intestinal group 2 innate lymphoid cells in asthma

  • Nat Commun. 2024 Sep 8;15(1):7850. doi: 10.1038/s41467-024-52252-2.
Kaifan Bao  1  2 ,  Xiaoqun Gu  3 ,  Yajun Song  3 ,  Yijing Zhou  3 ,  Yanyan Chen  3 ,  Xi Yu  4 ,  Weiyuan Yuan  3 ,  Liyun Shi  5 ,  Jie Zheng  6  7 ,  Min Hong  8
Affiliations
  • 1. Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China. [email protected].
  • 2. Department of Immunology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China. [email protected].
  • 3. Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
  • 4. Nanjing Haikerui Pharmaceutical Technology Co., LTD, Nanjing, 210023, China.
  • 5. Department of Immunology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
  • 6. Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China. [email protected].
  • 7. Department of Pharmacology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China. [email protected].
  • 8. Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China. [email protected].
PMID: 39245681 DOI: 10.1038/s41467-024-52252-2
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.

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