Identification of a unique subset of tissue-resident memory CD4+ T cells in Crohn's disease

Takehito Yokoi, Mari Murakami, Takako Kihara, Shigeto Seno, Mitsuru Arase, James Badger Wing, Jonas Nørskov Søndergaard, Ryuichi Kuwahara, Tomohiro Minagawa, Eri Oguro-Igashira, Daisuke Motooka, Daisuke Okuzaki, Ryota Mori, Atsuyo Ikeda, Yuki Sekido, Takahiro Amano, Hideki Iijima, Keiichi Ozono, Tsunekazu Mizushima, Seiichi HirotaHiroki Ikeuchi, Kiyoshi Takeda*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

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+ tissue-resident memory T cell (Trm) subset that is increased in Crohn's disease (CD) showing unique inflammatory properties. Functionally and transcriptionally distinct CD4+ Trm subsets are observed in the inflamed gut mucosa, among which a CD-specific CD4+ 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+ Trm subset is the most predominant producer of type 1 inflammatory cytokines upon various stimulations among all CD4+ 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.

Original languageEnglish
Article numbere2204269120
JournalProceedings of the National Academy of Sciences of the United States of America
Volume120
Issue number1
DOIs
StatePublished - 2023/01/03

Keywords

  • T-cell immunity
  • inflammatory bowel disease
  • mass cytometry
  • single-cell RNA-seq
  • tissue-resident T cell

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Identification of a unique subset of tissue-resident memory CD4+ T cells in Crohn's disease'. Together they form a unique fingerprint.

Cite this