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Downregulation of chemokine receptor 9 facilitates CD4+CD8αα+ intraepithelial lymphocyte development

Author

Listed:
  • Keiko Ono

    (Keio University School of Medicine)

  • Tomohisa Sujino

    (Keio University School of Medicine)

  • Kentaro Miyamoto

    (Keio University School of Medicine
    Miyarisan Pharmaceutical Co.)

  • Yosuke Harada

    (Keio University School of Medicine)

  • Satoshi Kojo

    (RIKEN Center for Integrative Medical Sciences
    Kanazawa University)

  • Yusuke Yoshimatsu

    (Keio University School of Medicine)

  • Shun Tanemoto

    (Keio University School of Medicine)

  • Yuzo Koda

    (Keio University School of Medicine
    Mitsubishi Tanabe Pharma Corporation)

  • Jiawen Zheng

    (RIKEN Center for Integrative Medical Sciences)

  • Kazutoshi Sayama

    (Shizuoka University)

  • Tsuyoshi Koide

    (National Institute of Genetics)

  • Toshiaki Teratani

    (Keio University School of Medicine)

  • Yohei Mikami

    (Keio University School of Medicine)

  • Kaoru Takabayashi

    (Keio University School of Medicine)

  • Nobuhiro Nakamoto

    (Keio University School of Medicine)

  • Naoki Hosoe

    (Keio University School of Medicine)

  • Mariya London

    (The Rockefeller University)

  • Haruhiko Ogata

    (Keio University School of Medicine)

  • Daniel Mucida

    (The Rockefeller University
    The Rockefeller University)

  • Ichiro Taniuchi

    (RIKEN Center for Integrative Medical Sciences)

  • Takanori Kanai

    (Keio University School of Medicine)

Abstract

Intestinal intraepithelial lymphocytes (IELs) reside in the gut epithelial layer, where they help in maintaining intestinal homeostasis. Peripheral CD4+ T cells can develop into CD4+CD8αα+ IELs upon arrival at the gut epithelium via the lamina propria (LP). Although this specific differentiation of T cells is well established, the mechanisms preventing it from occurring in the LP remain unclear. Here, we show that chemokine receptor 9 (CCR9) expression is low in epithelial CD4+CD8αα+ IELs, but CCR9 deficiency results in CD4+CD8αα+ over-differentiation in both the epithelium and the LP. Single-cell RNA sequencing shows an enriched precursor cell cluster for CD4+CD8αα+ IELs in Ccr9−/− mice. CD4+ T cells isolated from the epithelium of Ccr9−/− mice also display increased expression of Cbfβ2, and the genomic occupancy modification of Cbfβ2 expression reveals its important function in CD4+CD8αα+ differentiation. These results implicate a link between CCR9 downregulation and Cbfb2 splicing upregulation to enhance CD4+CD8αα+ IEL differentiation.

Suggested Citation

  • Keiko Ono & Tomohisa Sujino & Kentaro Miyamoto & Yosuke Harada & Satoshi Kojo & Yusuke Yoshimatsu & Shun Tanemoto & Yuzo Koda & Jiawen Zheng & Kazutoshi Sayama & Tsuyoshi Koide & Toshiaki Teratani & Y, 2023. "Downregulation of chemokine receptor 9 facilitates CD4+CD8αα+ intraepithelial lymphocyte development," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40950-2
    DOI: 10.1038/s41467-023-40950-2
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    References listed on IDEAS

    as
    1. Satoshi Kojo & Hirokazu Tanaka & Takaho A. Endo & Sawako Muroi & Ye Liu & Wooseok Seo & Mari Tenno & Kiyokazu Kakugawa & Yoshinori Naoe & Krutula Nair & Kazuyo Moro & Yoshinori Katsuragi & Akinori Kan, 2017. "Priming of lineage-specifying genes by Bcl11b is required for lineage choice in post-selection thymocytes," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
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