Identification of a unique subset of tissue-resident memory CD4 <sup>+</sup> T cells in Crohn’s disease

DOI Web Site 参考文献69件 オープンアクセス
  • Takehito Yokoi
    Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
  • Mari Murakami
    Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
  • Takako Kihara
    Department of Surgical Pathology, Hyogo College of Medicine, Hyogo 663-8501, Japan
  • Shigeto Seno
    Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, Osaka 565-0871, Japan
  • Mitsuru Arase
    Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
  • James Badger Wing
    Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan
  • Jonas Nørskov Søndergaard
    Center for Infectious Disease Education and Research, Osaka University, Osaka 565-0871, Japan
  • Ryuichi Kuwahara
    Department of Inflammatory Bowel Disease, Division of Surgery, Hyogo College of Medicine, Hyogo 663-8501, Japan
  • Tomohiro Minagawa
    Department of Inflammatory Bowel Disease, Division of Surgery, Hyogo College of Medicine, Hyogo 663-8501, Japan
  • Eri Oguro-Igashira
    Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
  • Daisuke Motooka
    Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan
  • Daisuke Okuzaki
    Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan
  • Ryota Mori
    Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
  • Atsuyo Ikeda
    Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
  • Yuki Sekido
    Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
  • Takahiro Amano
    Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
  • Hideki Iijima
    Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
  • Keiichi Ozono
    Department of Pediatrics, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
  • Tsunekazu Mizushima
    Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
  • Seiichi Hirota
    Department of Surgical Pathology, Hyogo College of Medicine, Hyogo 663-8501, Japan
  • Hiroki Ikeuchi
    Department of Inflammatory Bowel Disease, Division of Surgery, Hyogo College of Medicine, Hyogo 663-8501, Japan
  • Kiyoshi Takeda
    Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan

抄録

<jats:p> T cells differentiate into highly diverse subsets and display plasticity depending on the environment. Although lymphocytes are key mediators of inflammation, functional specialization of T cells in inflammatory bowel disease (IBD) has not been effectively described. Here, we performed deep profiling of T cells in the intestinal mucosa of IBD and identified a CD4 <jats:sup>+</jats:sup> tissue-resident memory T cell (Trm) subset that is increased in Crohn’s disease (CD) showing unique inflammatory properties. Functionally and transcriptionally distinct CD4 <jats:sup>+</jats:sup> Trm subsets are observed in the inflamed gut mucosa, among which a CD-specific CD4 <jats:sup>+</jats:sup> Trm subset, expressing CD161 and CCR5 along with CD103, displays previously unrecognized pleiotropic signatures of innate and effector activities. These inflammatory features are further enhanced by their spatial proximity to gut epithelial cells. Furthermore, the CD-specific CD4 <jats:sup>+</jats:sup> Trm subset is the most predominant producer of type 1 inflammatory cytokines upon various stimulations among all CD4 <jats:sup>+</jats:sup> T cells, suggesting that the accumulation of this T cell subset is a pathological hallmark of CD. Our results provide comprehensive insights into the pathogenesis of IBD, paving the way for decoding of the molecular mechanisms underlying this disease. </jats:p>

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