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Heterogeneity and clonal relationships of adaptive immune cells in ulcerative colitis revealed by single-cell analyses.
Boland, Brigid S; He, Zhaoren; Tsai, Matthew S; Olvera, Jocelyn G; Omilusik, Kyla D; Duong, Han G; Kim, Eleanor S; Limary, Abigail E; Jin, Wenhao; Milner, J Justin; Yu, Bingfei; Patel, Shefali A; Louis, Tiani L; Tysl, Tiffani; Kurd, Nadia S; Bortnick, Alexandra; Quezada, Lauren K; Kanbar, Jad N; Miralles, Ara; Huylebroeck, Danny; Valasek, Mark A; Dulai, Parambir S; Singh, Siddharth; Lu, Li-Fan; Bui, Jack D; Murre, Cornelis; Sandborn, William J; Goldrath, Ananda W; Yeo, Gene W; Chang, John T.
Affiliation
  • Boland BS; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • He Z; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Tsai MS; Division of Biologic Sciences, University of California, San Diego, La Jolla, CA, USA.
  • Olvera JG; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Omilusik KD; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Duong HG; Division of Biologic Sciences, University of California, San Diego, La Jolla, CA, USA.
  • Kim ES; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Limary AE; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Jin W; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Milner JJ; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Yu B; Division of Biologic Sciences, University of California, San Diego, La Jolla, CA, USA.
  • Patel SA; Division of Biologic Sciences, University of California, San Diego, La Jolla, CA, USA.
  • Louis TL; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Tysl T; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Kurd NS; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Bortnick A; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Quezada LK; Division of Biologic Sciences, University of California, San Diego, La Jolla, CA, USA.
  • Kanbar JN; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Miralles A; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Huylebroeck D; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Valasek MA; Department of Development and Regeneration, University of Leuven, Leuven, Belgium.
  • Dulai PS; Department of Cell Biology, Erasmus University Medical Center Rotterdam, 3015 CN Rotterdam, Netherlands.
  • Singh S; Department of Pathology, University of California, San Diego, La Jolla, CA, USA.
  • Lu LF; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Bui JD; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Murre C; Division of Biologic Sciences, University of California, San Diego, La Jolla, CA, USA.
  • Sandborn WJ; Department of Pathology, University of California, San Diego, La Jolla, CA, USA.
  • Goldrath AW; Division of Biologic Sciences, University of California, San Diego, La Jolla, CA, USA.
  • Yeo GW; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Chang JT; Division of Biologic Sciences, University of California, San Diego, La Jolla, CA, USA.
Sci Immunol ; 5(50)2020 08 21.
Article in En | MEDLINE | ID: mdl-32826341
ABSTRACT
Inflammatory bowel disease (IBD) encompasses a spectrum of gastrointestinal disorders driven by dysregulated immune responses against gut microbiota. We integrated single-cell RNA and antigen receptor sequencing to elucidate key components, cellular states, and clonal relationships of the peripheral and gastrointestinal mucosal immune systems in health and ulcerative colitis (UC). UC was associated with an increase in IgG1+ plasma cells in colonic tissue, increased colonic regulatory T cells characterized by elevated expression of the transcription factor ZEB2, and an enrichment of a γδ T cell subset in the peripheral blood. Moreover, we observed heterogeneity in CD8+ tissue-resident memory T (TRM) cells in colonic tissue, with four transcriptionally distinct states of differentiation observed across health and disease. In the setting of UC, there was a marked shift of clonally related CD8+ TRM cells toward an inflammatory state, mediated, in part, by increased expression of the T-box transcription factor Eomesodermin. Together, these results provide a detailed atlas of transcriptional changes occurring in adaptive immune cells in the context of UC and suggest a role for CD8+ TRM cells in IBD.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Colitis, Ulcerative / T-Lymphocytes, Regulatory / Intraepithelial Lymphocytes / Memory T Cells Limits: Animals / Humans / Male Language: En Journal: Sci Immunol Year: 2020 Document type: Article Affiliation country: Estados Unidos Publication country: EEUU / ESTADOS UNIDOS / ESTADOS UNIDOS DA AMERICA / EUA / UNITED STATES / UNITED STATES OF AMERICA / US / USA
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Colitis, Ulcerative / T-Lymphocytes, Regulatory / Intraepithelial Lymphocytes / Memory T Cells Limits: Animals / Humans / Male Language: En Journal: Sci Immunol Year: 2020 Document type: Article Affiliation country: Estados Unidos Publication country: EEUU / ESTADOS UNIDOS / ESTADOS UNIDOS DA AMERICA / EUA / UNITED STATES / UNITED STATES OF AMERICA / US / USA