Sterile activation of invariant natural killer T cells by ER-stressed antigen-presenting cells.


Journal

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876

Informations de publication

Date de publication:
19 11 2019
Historique:
pubmed: 7 11 2019
medline: 21 4 2020
entrez: 7 11 2019
Statut: ppublish

Résumé

Invariant NKT (iNKT) cells have the unique ability to shape immunity during antitumor immune responses and other forms of sterile and nonsterile inflammation. Recent studies have highlighted a variety of classes of endogenous and pathogen-derived lipid antigens that can trigger iNKT cell activation under sterile and nonsterile conditions. However, the context and mechanisms that drive the presentation of self-lipid antigens in sterile inflammation remain unclear. Here we report that endoplasmic reticulum (ER)-stressed myeloid cells, via signaling events modulated by the protein kinase RNA-like ER kinase (PERK) pathway, increase CD1d-mediated presentation of immunogenic endogenous lipid species, which results in enhanced iNKT cell activation both in vitro and in vivo. In addition, we demonstrate that actin cytoskeletal reorganization during ER stress results in an altered distribution of CD1d on the cell surface, which contributes to enhanced iNKT cell activation. These results define a previously unidentified mechanism that controls iNKT cell activation during sterile inflammation.

Identifiants

pubmed: 31690657
pii: 1910097116
doi: 10.1073/pnas.1910097116
pmc: PMC6876220
doi:

Substances chimiques

Antigens, CD1d 0
Autoantigens 0
CD1D protein, human 0
CD1d antigen, mouse 0
Glycosphingolipids 0
IL2RA protein, human 0
Interleukin-2 Receptor alpha Subunit 0
Lipids 0
Thapsigargin 67526-95-8
EIF2AK3 protein, human EC 2.7.11.1
eIF-2 Kinase EC 2.7.11.1

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

23671-23681

Subventions

Organisme : Medical Research Council
ID : MC_PC_15002
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : R01 DK088199
Pays : United States
Organisme : Cancer Research UK
ID : C399/A2291
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1000800
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1001750
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 104924/14/Z/14
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0700851
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12010/9
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0800158
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U137884181
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0400421
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12010/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00008/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K01577X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0501975
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00008/9
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 11331
Pays : United Kingdom
Organisme : NICHD NIH HHS
ID : K12 HD000850
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK034854
Pays : United States
Organisme : Wellcome Trust
ID : 202834/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K021222/1
Pays : United Kingdom

Informations de copyright

Copyright © 2019 the Author(s). Published by PNAS.

Déclaration de conflit d'intérêts

The authors declare no competing interest.

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Auteurs

Melissa Bedard (M)

Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom.

Dilip Shrestha (D)

Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom.

David A Priestman (DA)

Department of Pharmacology, University of Oxford, OX1 3QT Oxford, United Kingdom.

Yuting Wang (Y)

Center for Regenerative Therapies, Technische Universität Dresden, 01307 Dresden, Germany.
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.

Falk Schneider (F)

Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom.

Juan D Matute (JD)

Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital Harvard Medical School, Boston, MA 02115.
Division of Neonatology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.

Shankar S Iyer (SS)

Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital Harvard Medical School, Boston, MA 02115.

Uzi Gileadi (U)

Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom.

Gennaro Prota (G)

Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom.

Matheswaran Kandasamy (M)

Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom.

Natacha Veerapen (N)

School of Biosciences, University of Birmingham, B15 2TT Egdbaston, United Kingdom.

Gurdyal Besra (G)

School of Biosciences, University of Birmingham, B15 2TT Egdbaston, United Kingdom.

Marco Fritzsche (M)

Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom.
Kennedy Institute for Rheumatology, University of Oxford, OX3 7LF Oxford, United Kingdom.

Sebastian Zeissig (S)

Center for Regenerative Therapies, Technische Universität Dresden, 01307 Dresden, Germany.
Department of Medicine I, University Medical Center Dresden, Technische Universität Dresden, 01307 Dresden, Germany.

Andrej Shevchenko (A)

Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.

John C Christianson (JC)

Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Science, University of Oxford, OX3 7LD Oxford, United Kingdom.

Frances M Platt (FM)

Department of Pharmacology, University of Oxford, OX1 3QT Oxford, United Kingdom.

Christian Eggeling (C)

Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom.
Institute of Applied Optics and Biophysics, 07743 Jena, Germany.
Department of Biophysical Imaging, Leibniz Institute of Photonic Technologies e.V., 07745 Jena, Germany.

Richard S Blumberg (RS)

Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital Harvard Medical School, Boston, MA 02115.

Mariolina Salio (M)

Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom.

Vincenzo Cerundolo (V)

Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom; vincenzo.cerundolo@imm.ox.ac.uk.

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Classifications MeSH