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

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  • Kaifan Bao

    (School of Pharmacy, Nanjing University of Chinese Medicine
    Nanjing University of Chinese Medicine)

  • Xiaoqun Gu

    (School of Pharmacy, Nanjing University of Chinese Medicine)

  • Yajun Song

    (School of Pharmacy, Nanjing University of Chinese Medicine)

  • Yijing Zhou

    (School of Pharmacy, Nanjing University of Chinese Medicine)

  • Yanyan Chen

    (School of Pharmacy, Nanjing University of Chinese Medicine)

  • Xi Yu

    (LTD)

  • Weiyuan Yuan

    (School of Pharmacy, Nanjing University of Chinese Medicine)

  • Liyun Shi

    (Nanjing University of Chinese Medicine)

  • Jie Zheng

    (School of Pharmacy, Nanjing University of Chinese Medicine
    Nanjing University of Chinese Medicine)

  • Min Hong

    (School of Pharmacy, Nanjing University of Chinese Medicine)

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.

Suggested Citation

  • Kaifan Bao & Xiaoqun Gu & Yajun Song & Yijing Zhou & Yanyan Chen & Xi Yu & Weiyuan Yuan & Liyun Shi & Jie Zheng & Min Hong, 2024. "TCF-1 and TOX regulate the memory formation of intestinal group 2 innate lymphoid cells in asthma," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52252-2
    DOI: 10.1038/s41467-024-52252-2
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