Identification of a unique subset of tissue-resident memory CD4 <sup>+</sup> T cells in Crohn’s disease
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- Takehito Yokoi
- Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
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- Mari Murakami
- Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
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- Takako Kihara
- Department of Surgical Pathology, Hyogo College of Medicine, Hyogo 663-8501, Japan
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- Shigeto Seno
- Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, Osaka 565-0871, Japan
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- Mitsuru Arase
- Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
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- James Badger Wing
- Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan
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- Jonas Nørskov Søndergaard
- Center for Infectious Disease Education and Research, Osaka University, Osaka 565-0871, Japan
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- Ryuichi Kuwahara
- Department of Inflammatory Bowel Disease, Division of Surgery, Hyogo College of Medicine, Hyogo 663-8501, Japan
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- Tomohiro Minagawa
- Department of Inflammatory Bowel Disease, Division of Surgery, Hyogo College of Medicine, Hyogo 663-8501, Japan
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- Eri Oguro-Igashira
- Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
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- Daisuke Motooka
- Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan
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- Daisuke Okuzaki
- Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan
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- Ryota Mori
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
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- Atsuyo Ikeda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
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- Yuki Sekido
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
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- Takahiro Amano
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
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- Hideki Iijima
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
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- Keiichi Ozono
- Department of Pediatrics, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
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- Tsunekazu Mizushima
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
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- Seiichi Hirota
- Department of Surgical Pathology, Hyogo College of Medicine, Hyogo 663-8501, Japan
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- Hiroki Ikeuchi
- Department of Inflammatory Bowel Disease, Division of Surgery, Hyogo College of Medicine, Hyogo 663-8501, Japan
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- 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>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 120 (1), 2022-12-27
Proceedings of the National Academy of Sciences
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詳細情報 詳細情報について
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- CRID
- 1360580229813854208
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- ISSN
- 10916490
- 00278424
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- データソース種別
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- Crossref
- KAKEN