Tissue alarmins and adaptive cytokine induce dynamic and distinct transcriptional responses in tissue-resident intraepithelial cytotoxic T lymphocytes.

Alarmins / metabolism Autoimmunity Celiac Disease / etiology Cytokines / metabolism Gene Expression Profiling Gene Expression Regulation Humans Inflammatory Bowel Diseases / etiology Interleukin-15 / metabolism Intestinal Mucosa / immunology Intraepithelial Lymphocytes / immunology Promoter Regions, Genetic T-Lymphocytes, Cytotoxic / immunology
Autoimmune disease Cytotoxic T lymphocytes IFNβ IL-15 IL-21 Intraepithelial lymphocytes Tissue-resident lymphocytes

Journal

Journal of autoimmunity
ISSN: 1095-9157
Titre abrégé: J Autoimmun
Pays: England
ID NLM: 8812164

Informations de publication

Date de publication:
03 2020
Historique:
received: 10 11 2019
revised: 28 01 2020
accepted: 28 01 2020
pubmed: 9 2 2020
medline: 6 7 2021
entrez: 9 2 2020
Statut: ppublish

Résumé

The respective effects of tissue alarmins interleukin (IL)-15 and interferon beta (IFNβ), and IL-21 produced by T cells on the reprogramming of cytotoxic T lymphocytes (CTLs) that cause tissue destruction in celiac disease is poorly understood. Transcriptomic and epigenetic profiling of primary intestinal CTLs showed massive and distinct temporal transcriptional changes in response to tissue alarmins, while the impact of IL-21 was limited. Only anti-viral pathways were induced in response to all the three stimuli, albeit with differences in dynamics and strength. Moreover, changes in gene expression were primarily independent of changes in H3K27ac, suggesting that other regulatory mechanisms drive the robust transcriptional response. Finally, we found that IL-15/IFNβ/IL-21 transcriptional signatures could be linked to transcriptional alterations in risk loci for complex immune diseases. Together these results provide new insights into molecular mechanisms that fuel the activation of CTLs under conditions that emulate the inflammatory environment in patients with autoimmune diseases.

Identifiants

DOI: 10.1016/j.jaut.2020.102422 PMID: 32033836 PMC: PMC7049906
pubmed: 32033836
pii: S0896-8411(20)30033-0
doi: 10.1016/j.jaut.2020.102422
pmc: PMC7049906
pii:
doi:

Substances chimiques

Alarmins 0
Cytokines 0
IL15 protein, human 0
Interleukin-15 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

102422

Subventions

Organisme : NCI NIH HHS
ID : P30 CA014599
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007090
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK098435
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK067180
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK042086
Pays : United States

Informations de copyright

Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest B. J. is an advisor to Immusan T, BIONIZ therapeutics and Actobio therapeutics.

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Auteurs

Maria Magdalena Zorro (MM)

Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Raul Aguirre-Gamboa (R)

Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Toufic Mayassi (T)

Department of Medicine, University of Chicago, Chicago, USA; Committee on Immunology, University of Chicago, Chicago, USA.

Cezary Ciszewski (C)

Department of Medicine, University of Chicago, Chicago, USA.

Donatella Barisani (D)

School of Medicine and Surgery, University of Milano-Bicocca, Italy.

Shixian Hu (S)

Department of Gastroenterology and Hepatology, University Medical Center, Groningen, University of Groningen, Groningen, the Netherlands.

Rinse K Weersma (RK)

Department of Gastroenterology and Hepatology, University Medical Center, Groningen, University of Groningen, Groningen, the Netherlands.

Sebo Withoff (S)

Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Yang Li (Y)

Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands; Department of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine, Helmholtz Centre for Infection Research, Hannover Medical School. Hannover, Germany.

Cisca Wijmenga (C)

Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; K.G. Jebsen Coeliac Disease Research Centre, Department of Immunology, University of Oslo, Oslo, Norway.

Bana Jabri (B)

Department of Medicine, University of Chicago, Chicago, USA; Committee on Immunology, University of Chicago, Chicago, USA. Electronic address: bjabri@bsd.uchicago.edu.

Iris H Jonkers (IH)

Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; K.G. Jebsen Coeliac Disease Research Centre, Department of Immunology, University of Oslo, Oslo, Norway. Electronic address: i.h.jonkers@umcg.nl.

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Classifications MeSH

questionsmedicales.fr › Facteurs biologiques › Médiateurs de l'inflammation › Alarmines › Tissue alarmins and adaptive cytokine induce...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunité › Auto-immunité › Tissue alarmins and adaptive cytokine induce...
questionsmedicales.fr › Maladies métaboliques et nutritionnelles › Maladies métaboliques › Syndromes de malabsorption › Maladie coeliaque › Tissue alarmins and adaptive cytokine induce...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Tissue alarmins and adaptive cytokine induce...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › Tissue alarmins and adaptive cytokine induce...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Tissue alarmins and adaptive cytokine induce...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Tissue alarmins and adaptive cytokine induce...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Maladies inflammatoires intestinales › Tissue alarmins and adaptive cytokine induce...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interleukines › Interleukine-15 › Tissue alarmins and adaptive cytokine induce...
questionsmedicales.fr › Tissus › Membranes › Muqueuse › Muqueuse intestinale › Tissue alarmins and adaptive cytokine induce...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Sous-populations de lymphocytes T › Lymphocytes intra-épithéliaux › Tissue alarmins and adaptive cytokine induce...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Composants de gène › Éléments de régulation transcriptionnelle › Régions promotrices (génétique) › Tissue alarmins and adaptive cytokine induce...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Sous-populations de lymphocytes T › Lymphocytes T cytotoxiques › Tissue alarmins and adaptive cytokine induce...