First Authors | Melissa Bedard |
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Authors | Melissa Bedard, Dilip Shrestha, David A Priestman, Yuting Wang, Falk Schneider, Juan D Matute, Shankar S Iyer, Uzi Gileadi, Gennaro Prota, Matheswaran Kandasamy, Natacha Veerapen, Gurdyal Besra, Marco Fritzsche, Sebastian Zeissig, Andrej Shevchenko, John C Christianson, Frances Platt, Christian Eggeling, Richard S Blumberg, Mariolina Salio, Vincenzo Cerundolo |
Corresponding Authors | Vincenzo Cerundolo |
Last Authors | Vincenzo Cerundolo |
Journal Name | Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U.S.A.) |
Volume | 116 |
Issue | 47 |
Page Range | 23671-23681 |
Open Access | true |
Print Publication Date | 2019-11-19 |
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Abstract | 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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Affiliated With | Shevchenko |
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Publication Status | Published |
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DOI | 10.1073/pnas.1910097116 |
PubMed ID | 31690657 |
WebOfScience Link | WOS:000498683000047 |
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Created By | thuem |
Added Date | 2019-11-12 |
Last Edited By | herbst |
Last Edited Date | 2021-04-29 17:48:14.604 |
Library ID | 7539 |
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Entry Complete | true |
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Include in Edoc Report | true |
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