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

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...

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Autores principales: Bedard, Melissa, Shrestha, Dilip, Priestman, David A., Wang, Yuting, Schneider, Falk, Matute, Juan D., Iyer, Shankar S., Gileadi, Uzi, Prota, Gennaro, Kandasamy, Matheswaran, Veerapen, Natacha, Besra, Gurdyal, Fritzsche, Marco, Zeissig, Sebastian, Shevchenko, Andrej, Christianson, John C., Platt, Frances M., Eggeling, Christian, Blumberg, Richard S., Salio, Mariolina, Cerundolo, Vincenzo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6876220/
https://www.ncbi.nlm.nih.gov/pubmed/31690657
http://dx.doi.org/10.1073/pnas.1910097116
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author Bedard, Melissa
Shrestha, Dilip
Priestman, David A.
Wang, Yuting
Schneider, Falk
Matute, Juan D.
Iyer, Shankar S.
Gileadi, Uzi
Prota, Gennaro
Kandasamy, Matheswaran
Veerapen, Natacha
Besra, Gurdyal
Fritzsche, Marco
Zeissig, Sebastian
Shevchenko, Andrej
Christianson, John C.
Platt, Frances M.
Eggeling, Christian
Blumberg, Richard S.
Salio, Mariolina
Cerundolo, Vincenzo
author_facet Bedard, Melissa
Shrestha, Dilip
Priestman, David A.
Wang, Yuting
Schneider, Falk
Matute, Juan D.
Iyer, Shankar S.
Gileadi, Uzi
Prota, Gennaro
Kandasamy, Matheswaran
Veerapen, Natacha
Besra, Gurdyal
Fritzsche, Marco
Zeissig, Sebastian
Shevchenko, Andrej
Christianson, John C.
Platt, Frances M.
Eggeling, Christian
Blumberg, Richard S.
Salio, Mariolina
Cerundolo, Vincenzo
author_sort Bedard, Melissa
collection PubMed
description 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.
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spelling pubmed-68762202019-11-29 Sterile activation of invariant natural killer T cells by ER-stressed antigen-presenting cells Bedard, Melissa Shrestha, Dilip Priestman, David A. Wang, Yuting Schneider, Falk Matute, Juan D. Iyer, Shankar S. Gileadi, Uzi Prota, Gennaro Kandasamy, Matheswaran Veerapen, Natacha Besra, Gurdyal Fritzsche, Marco Zeissig, Sebastian Shevchenko, Andrej Christianson, John C. Platt, Frances M. Eggeling, Christian Blumberg, Richard S. Salio, Mariolina Cerundolo, Vincenzo Proc Natl Acad Sci U S A PNAS Plus 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. National Academy of Sciences 2019-11-19 2019-11-05 /pmc/articles/PMC6876220/ /pubmed/31690657 http://dx.doi.org/10.1073/pnas.1910097116 Text en Copyright © 2019 the Author(s). Published by PNAS. http://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle PNAS Plus
Bedard, Melissa
Shrestha, Dilip
Priestman, David A.
Wang, Yuting
Schneider, Falk
Matute, Juan D.
Iyer, Shankar S.
Gileadi, Uzi
Prota, Gennaro
Kandasamy, Matheswaran
Veerapen, Natacha
Besra, Gurdyal
Fritzsche, Marco
Zeissig, Sebastian
Shevchenko, Andrej
Christianson, John C.
Platt, Frances M.
Eggeling, Christian
Blumberg, Richard S.
Salio, Mariolina
Cerundolo, Vincenzo
Sterile activation of invariant natural killer T cells by ER-stressed antigen-presenting cells
title Sterile activation of invariant natural killer T cells by ER-stressed antigen-presenting cells
title_full Sterile activation of invariant natural killer T cells by ER-stressed antigen-presenting cells
title_fullStr Sterile activation of invariant natural killer T cells by ER-stressed antigen-presenting cells
title_full_unstemmed Sterile activation of invariant natural killer T cells by ER-stressed antigen-presenting cells
title_short Sterile activation of invariant natural killer T cells by ER-stressed antigen-presenting cells
title_sort sterile activation of invariant natural killer t cells by er-stressed antigen-presenting cells
topic PNAS Plus
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6876220/
https://www.ncbi.nlm.nih.gov/pubmed/31690657
http://dx.doi.org/10.1073/pnas.1910097116
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