Exhaustion of CD39-Expressing CD8


Journal

Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630

Informations de publication

Date de publication:
10 2022
Historique:
received: 03 10 2021
revised: 07 06 2022
accepted: 14 06 2022
pubmed: 24 6 2022
medline: 28 9 2022
entrez: 23 6 2022
Statut: ppublish

Résumé

Exhaustion of CD8 T cells has been suggested to inform different clinical outcomes in Crohn's disease, but detailed analyses are lacking. This study aimed to identify the role of exhaustion on a single-cell level and identify relevant CD8 T cell populations in Crohn's disease. Blood and intestinal tissue from 58 patients with Crohn's disease (active disease or remission) were assessed for CD8 T cell expression of exhaustion markers and their cytokine profile by highly multiplexed flow and mass cytometry. Key disease-associated subsets were sorted and analyzed by RNA sequencing. CD39 inhibition assays were performed in vitro. Activated CD39 These data showed a role for the exhaustion of peripheral CD39-expressing CD8 T cell subsets in Crohn's disease. Their low frequency illustrated the utility of single-cell cytometry methods for identification of relevant immune populations. Importantly, the link of their exhaustion status to the clinical activity and their specific gene signatures have implications for exhaustion-based personalized medicine approaches.

Sections du résumé

BACKGROUND & AIMS
Exhaustion of CD8 T cells has been suggested to inform different clinical outcomes in Crohn's disease, but detailed analyses are lacking. This study aimed to identify the role of exhaustion on a single-cell level and identify relevant CD8 T cell populations in Crohn's disease.
METHODS
Blood and intestinal tissue from 58 patients with Crohn's disease (active disease or remission) were assessed for CD8 T cell expression of exhaustion markers and their cytokine profile by highly multiplexed flow and mass cytometry. Key disease-associated subsets were sorted and analyzed by RNA sequencing. CD39 inhibition assays were performed in vitro.
RESULTS
Activated CD39
CONCLUSIONS
These data showed a role for the exhaustion of peripheral CD39-expressing CD8 T cell subsets in Crohn's disease. Their low frequency illustrated the utility of single-cell cytometry methods for identification of relevant immune populations. Importantly, the link of their exhaustion status to the clinical activity and their specific gene signatures have implications for exhaustion-based personalized medicine approaches.

Identifiants

pubmed: 35738329
pii: S0016-5085(22)00663-1
doi: 10.1053/j.gastro.2022.06.045
pii:
doi:

Substances chimiques

Biomarkers 0
Cytokines 0
Programmed Cell Death 1 Receptor 0
Apyrase EC 3.6.1.5
ENTPD1 protein, human EC 3.6.1.5

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

965-981.e31

Informations de copyright

Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.

Auteurs

Anna-Maria Globig (AM)

Clinic for Internal Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, University Medical Center Freiburg, Faculty of Medicine, Freiburg, Germany.

Lena Sophie Mayer (LS)

Clinic for Internal Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, University Medical Center Freiburg, Faculty of Medicine, Freiburg, Germany.

Maximilian Heeg (M)

Institute for Immunodeficiency, Center for Chronic Immunodeficiency, University Medical Center Freiburg, Faculty of Medicine, Freiburg, Germany.

Geoffroy Andrieux (G)

Institute of Medical Bioinformatics and Systems Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium Partner Site Freiburg, German Cancer Research Center, Heidelberg, Germany.

Manching Ku (M)

Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany.

Patricia Otto-Mora (P)

Clinic for Internal Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, University Medical Center Freiburg, Faculty of Medicine, Freiburg, Germany.

Anna Veronika Hipp (AV)

Clinic for Internal Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, University Medical Center Freiburg, Faculty of Medicine, Freiburg, Germany.

Katharina Zoldan (K)

Clinic for Internal Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, University Medical Center Freiburg, Faculty of Medicine, Freiburg, Germany.

Ajinkya Pattekar (A)

Department of Medicine, Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.

Nisha Rana (N)

Clinic for Internal Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, University Medical Center Freiburg, Faculty of Medicine, Freiburg, Germany.

Christoph Schell (C)

Institute for Surgical Pathology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.

Melanie Boerries (M)

Institute of Medical Bioinformatics and Systems Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium Partner Site Freiburg, German Cancer Research Center, Heidelberg, Germany.

Maike Hofmann (M)

Clinic for Internal Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, University Medical Center Freiburg, Faculty of Medicine, Freiburg, Germany.

Christoph Neumann-Haefelin (C)

Clinic for Internal Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, University Medical Center Freiburg, Faculty of Medicine, Freiburg, Germany.

Armin Kuellmer (A)

Clinic for Internal Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, University Medical Center Freiburg, Faculty of Medicine, Freiburg, Germany.

Arthur Schmidt (A)

Clinic for Internal Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, University Medical Center Freiburg, Faculty of Medicine, Freiburg, Germany.

Tobias Boettler (T)

Clinic for Internal Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, University Medical Center Freiburg, Faculty of Medicine, Freiburg, Germany.

Vesselin Tomov (V)

Department of Medicine, Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.

Robert Thimme (R)

Clinic for Internal Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, University Medical Center Freiburg, Faculty of Medicine, Freiburg, Germany.

Peter Hasselblatt (P)

Clinic for Internal Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, University Medical Center Freiburg, Faculty of Medicine, Freiburg, Germany.

Bertram Bengsch (B)

Clinic for Internal Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, University Medical Center Freiburg, Faculty of Medicine, Freiburg, Germany; German Cancer Consortium Partner Site Freiburg, German Cancer Research Center, Heidelberg, Germany; Centre for Biological Signalling Studies (BIOSS) and Centre for Integrative Biological Signalling Studies (CIBSS), University of Freiburg, Freiburg, Germany. Electronic address: bertram.bengsch@uniklinik-freiburg.de.

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Classifications MeSH