TY - JOUR
T1 - Identification of a unique subset of tissue-resident memory CD4+ T cells in Crohn's disease
AU - Yokoi, Takehito
AU - Murakami, Mari
AU - Kihara, Takako
AU - Seno, Shigeto
AU - Arase, Mitsuru
AU - Wing, James Badger
AU - Søndergaard, Jonas Nørskov
AU - Kuwahara, Ryuichi
AU - Minagawa, Tomohiro
AU - Oguro-Igashira, Eri
AU - Motooka, Daisuke
AU - Okuzaki, Daisuke
AU - Mori, Ryota
AU - Ikeda, Atsuyo
AU - Sekido, Yuki
AU - Amano, Takahiro
AU - Iijima, Hideki
AU - Ozono, Keiichi
AU - Mizushima, Tsunekazu
AU - Hirota, Seiichi
AU - Ikeuchi, Hiroki
AU - Takeda, Kiyoshi
N1 - Publisher Copyright:
© 2022 the Author(s).
PY - 2023/1/3
Y1 - 2023/1/3
N2 - 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.
AB - 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.
KW - T-cell immunity
KW - inflammatory bowel disease
KW - mass cytometry
KW - single-cell RNA-seq
KW - tissue-resident T cell
UR - http://www.scopus.com/inward/record.url?scp=85144768073&partnerID=8YFLogxK
U2 - 10.1073/pnas.2204269120
DO - 10.1073/pnas.2204269120
M3 - 学術論文
C2 - 36574662
AN - SCOPUS:85144768073
SN - 0027-8424
VL - 120
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 1
M1 - e2204269120
ER -