ER stress in antigen‐presenting cells promotes NKT cell activation through endogenous neutral lipids
Abstract CD1d‐restricted invariant natural killer T (iNKT) cells constitute a common glycolipid‐reactive innate‐like T‐cell subset with a broad impact on innate and adaptive immunity. While several microbial glycolipids are known to activate iNKT cells, the cellular mechanisms leading to endogenous...
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| Autor*in: |
Govindarajan, Srinath [verfasserIn] Verheugen, Eveline [verfasserIn] Venken, Koen [verfasserIn] Gaublomme, Djoere [verfasserIn] Maelegheer, Margaux [verfasserIn] Cloots, Eva [verfasserIn] Gysens, Fien [verfasserIn] De Geest, Bruno G [verfasserIn] Cheng, Tan‐Yun [verfasserIn] Moody, D Branch [verfasserIn] Janssens, Sophie [verfasserIn] Drennan, Michael [verfasserIn] Elewaut, Dirk [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2020 |
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| Schlagwörter: |
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| Anmerkung: |
© The Author(s) 2020 |
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| Übergeordnetes Werk: |
Enthalten in: EMBO Reports - Nature Publishing Group UK, 2023, 21(2020), 6 vom: 03. Mai |
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| Übergeordnetes Werk: |
volume:21 ; year:2020 ; number:6 ; day:03 ; month:05 |
| Links: |
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| DOI / URN: |
10.15252/embr.201948927 |
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| Katalog-ID: |
SPR058177426 |
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| 100 | 1 | |a Govindarajan, Srinath |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a ER stress in antigen‐presenting cells promotes NKT cell activation through endogenous neutral lipids |
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| 520 | |a Abstract CD1d‐restricted invariant natural killer T (iNKT) cells constitute a common glycolipid‐reactive innate‐like T‐cell subset with a broad impact on innate and adaptive immunity. While several microbial glycolipids are known to activate iNKT cells, the cellular mechanisms leading to endogenous CD1d‐dependent glycolipid responses remain largely unclear. Here, we show that endoplasmic reticulum (ER) stress in APCs is a potent inducer of CD1d‐dependent iNKT cell autoreactivity. This pathway relies on the presence of two transducers of the unfolded protein response: inositol‐requiring enzyme‐1a (IRE1α) and protein kinase R‐like ER kinase (PERK). Surprisingly, the neutral but not the polar lipids generated within APCs undergoing ER stress are capable of activating iNKT cells. These data reveal that ER stress is an important mechanism to elicit endogenous CD1d‐restricted iNKT cell responses through induction of distinct classes of neutral lipids. | ||
| 520 | |a Synopsis Upon ER stress immunogenic lipids are produced that activate NKT cells. Defining the conditions required to generate endogenous high immunogenic lipid antigens paves the way for the design of novel lipids with immunomodulatory function. ER stress triggers IRE1α/PERK pathways to restore cellular homeostasis by generating distinct neutral and polar lipids.Neutral lipid species generated under these conditions are enriched and loaded onto CD1d to activate iNKT cells.Cytokines produced by iNKT cells during ER stress serve to activate the innate and adaptive immune system.ER stress is an important mechanism to elicit endogenous CD1d‐restricted iNKT cell responses. | ||
| 520 | |a Graphical Abstract Upon ER stress immunogenic lipids are produced that activate NKT cells. Defining the conditions required to generate endogenous high immunogenic lipid antigens paves the way for the design of novel lipids with immunomodulatory function. | ||
| 650 | 4 | |a antigen‐presenting cells |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a ER stress |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a lipid antigens |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a neutral lipid |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a NKT cells |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Verheugen, Eveline |e verfasserin |4 aut | |
| 700 | 1 | |a Venken, Koen |e verfasserin |4 aut | |
| 700 | 1 | |a Gaublomme, Djoere |e verfasserin |4 aut | |
| 700 | 1 | |a Maelegheer, Margaux |e verfasserin |4 aut | |
| 700 | 1 | |a Cloots, Eva |e verfasserin |4 aut | |
| 700 | 1 | |a Gysens, Fien |e verfasserin |4 aut | |
| 700 | 1 | |a De Geest, Bruno G |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Tan‐Yun |e verfasserin |4 aut | |
| 700 | 1 | |a Moody, D Branch |e verfasserin |4 aut | |
| 700 | 1 | |a Janssens, Sophie |e verfasserin |4 aut | |
| 700 | 1 | |a Drennan, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Elewaut, Dirk |e verfasserin |0 (orcid)0000-0003-3979-4824 |4 aut | |
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10.15252/embr.201948927 doi (DE-627)SPR058177426 (SPR)embr.201948927-e DE-627 ger DE-627 rakwb eng Govindarajan, Srinath verfasserin aut ER stress in antigen‐presenting cells promotes NKT cell activation through endogenous neutral lipids 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2020 Abstract CD1d‐restricted invariant natural killer T (iNKT) cells constitute a common glycolipid‐reactive innate‐like T‐cell subset with a broad impact on innate and adaptive immunity. While several microbial glycolipids are known to activate iNKT cells, the cellular mechanisms leading to endogenous CD1d‐dependent glycolipid responses remain largely unclear. Here, we show that endoplasmic reticulum (ER) stress in APCs is a potent inducer of CD1d‐dependent iNKT cell autoreactivity. This pathway relies on the presence of two transducers of the unfolded protein response: inositol‐requiring enzyme‐1a (IRE1α) and protein kinase R‐like ER kinase (PERK). Surprisingly, the neutral but not the polar lipids generated within APCs undergoing ER stress are capable of activating iNKT cells. These data reveal that ER stress is an important mechanism to elicit endogenous CD1d‐restricted iNKT cell responses through induction of distinct classes of neutral lipids. Synopsis Upon ER stress immunogenic lipids are produced that activate NKT cells. Defining the conditions required to generate endogenous high immunogenic lipid antigens paves the way for the design of novel lipids with immunomodulatory function. ER stress triggers IRE1α/PERK pathways to restore cellular homeostasis by generating distinct neutral and polar lipids.Neutral lipid species generated under these conditions are enriched and loaded onto CD1d to activate iNKT cells.Cytokines produced by iNKT cells during ER stress serve to activate the innate and adaptive immune system.ER stress is an important mechanism to elicit endogenous CD1d‐restricted iNKT cell responses. Graphical Abstract Upon ER stress immunogenic lipids are produced that activate NKT cells. Defining the conditions required to generate endogenous high immunogenic lipid antigens paves the way for the design of novel lipids with immunomodulatory function. antigen‐presenting cells (dpeaa)DE-He213 ER stress (dpeaa)DE-He213 lipid antigens (dpeaa)DE-He213 neutral lipid (dpeaa)DE-He213 NKT cells (dpeaa)DE-He213 Verheugen, Eveline verfasserin aut Venken, Koen verfasserin aut Gaublomme, Djoere verfasserin aut Maelegheer, Margaux verfasserin aut Cloots, Eva verfasserin aut Gysens, Fien verfasserin aut De Geest, Bruno G verfasserin aut Cheng, Tan‐Yun verfasserin aut Moody, D Branch verfasserin aut Janssens, Sophie verfasserin aut Drennan, Michael verfasserin aut Elewaut, Dirk verfasserin (orcid)0000-0003-3979-4824 aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 21(2020), 6 vom: 03. Mai (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:21 year:2020 number:6 day:03 month:05 https://dx.doi.org/10.15252/embr.201948927 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4315 GBV_ILN_4317 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 21 2020 6 03 05 |
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10.15252/embr.201948927 doi (DE-627)SPR058177426 (SPR)embr.201948927-e DE-627 ger DE-627 rakwb eng Govindarajan, Srinath verfasserin aut ER stress in antigen‐presenting cells promotes NKT cell activation through endogenous neutral lipids 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2020 Abstract CD1d‐restricted invariant natural killer T (iNKT) cells constitute a common glycolipid‐reactive innate‐like T‐cell subset with a broad impact on innate and adaptive immunity. While several microbial glycolipids are known to activate iNKT cells, the cellular mechanisms leading to endogenous CD1d‐dependent glycolipid responses remain largely unclear. Here, we show that endoplasmic reticulum (ER) stress in APCs is a potent inducer of CD1d‐dependent iNKT cell autoreactivity. This pathway relies on the presence of two transducers of the unfolded protein response: inositol‐requiring enzyme‐1a (IRE1α) and protein kinase R‐like ER kinase (PERK). Surprisingly, the neutral but not the polar lipids generated within APCs undergoing ER stress are capable of activating iNKT cells. These data reveal that ER stress is an important mechanism to elicit endogenous CD1d‐restricted iNKT cell responses through induction of distinct classes of neutral lipids. Synopsis Upon ER stress immunogenic lipids are produced that activate NKT cells. Defining the conditions required to generate endogenous high immunogenic lipid antigens paves the way for the design of novel lipids with immunomodulatory function. ER stress triggers IRE1α/PERK pathways to restore cellular homeostasis by generating distinct neutral and polar lipids.Neutral lipid species generated under these conditions are enriched and loaded onto CD1d to activate iNKT cells.Cytokines produced by iNKT cells during ER stress serve to activate the innate and adaptive immune system.ER stress is an important mechanism to elicit endogenous CD1d‐restricted iNKT cell responses. Graphical Abstract Upon ER stress immunogenic lipids are produced that activate NKT cells. Defining the conditions required to generate endogenous high immunogenic lipid antigens paves the way for the design of novel lipids with immunomodulatory function. antigen‐presenting cells (dpeaa)DE-He213 ER stress (dpeaa)DE-He213 lipid antigens (dpeaa)DE-He213 neutral lipid (dpeaa)DE-He213 NKT cells (dpeaa)DE-He213 Verheugen, Eveline verfasserin aut Venken, Koen verfasserin aut Gaublomme, Djoere verfasserin aut Maelegheer, Margaux verfasserin aut Cloots, Eva verfasserin aut Gysens, Fien verfasserin aut De Geest, Bruno G verfasserin aut Cheng, Tan‐Yun verfasserin aut Moody, D Branch verfasserin aut Janssens, Sophie verfasserin aut Drennan, Michael verfasserin aut Elewaut, Dirk verfasserin (orcid)0000-0003-3979-4824 aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 21(2020), 6 vom: 03. Mai (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:21 year:2020 number:6 day:03 month:05 https://dx.doi.org/10.15252/embr.201948927 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4315 GBV_ILN_4317 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 21 2020 6 03 05 |
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10.15252/embr.201948927 doi (DE-627)SPR058177426 (SPR)embr.201948927-e DE-627 ger DE-627 rakwb eng Govindarajan, Srinath verfasserin aut ER stress in antigen‐presenting cells promotes NKT cell activation through endogenous neutral lipids 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2020 Abstract CD1d‐restricted invariant natural killer T (iNKT) cells constitute a common glycolipid‐reactive innate‐like T‐cell subset with a broad impact on innate and adaptive immunity. While several microbial glycolipids are known to activate iNKT cells, the cellular mechanisms leading to endogenous CD1d‐dependent glycolipid responses remain largely unclear. Here, we show that endoplasmic reticulum (ER) stress in APCs is a potent inducer of CD1d‐dependent iNKT cell autoreactivity. This pathway relies on the presence of two transducers of the unfolded protein response: inositol‐requiring enzyme‐1a (IRE1α) and protein kinase R‐like ER kinase (PERK). Surprisingly, the neutral but not the polar lipids generated within APCs undergoing ER stress are capable of activating iNKT cells. These data reveal that ER stress is an important mechanism to elicit endogenous CD1d‐restricted iNKT cell responses through induction of distinct classes of neutral lipids. Synopsis Upon ER stress immunogenic lipids are produced that activate NKT cells. Defining the conditions required to generate endogenous high immunogenic lipid antigens paves the way for the design of novel lipids with immunomodulatory function. ER stress triggers IRE1α/PERK pathways to restore cellular homeostasis by generating distinct neutral and polar lipids.Neutral lipid species generated under these conditions are enriched and loaded onto CD1d to activate iNKT cells.Cytokines produced by iNKT cells during ER stress serve to activate the innate and adaptive immune system.ER stress is an important mechanism to elicit endogenous CD1d‐restricted iNKT cell responses. Graphical Abstract Upon ER stress immunogenic lipids are produced that activate NKT cells. Defining the conditions required to generate endogenous high immunogenic lipid antigens paves the way for the design of novel lipids with immunomodulatory function. antigen‐presenting cells (dpeaa)DE-He213 ER stress (dpeaa)DE-He213 lipid antigens (dpeaa)DE-He213 neutral lipid (dpeaa)DE-He213 NKT cells (dpeaa)DE-He213 Verheugen, Eveline verfasserin aut Venken, Koen verfasserin aut Gaublomme, Djoere verfasserin aut Maelegheer, Margaux verfasserin aut Cloots, Eva verfasserin aut Gysens, Fien verfasserin aut De Geest, Bruno G verfasserin aut Cheng, Tan‐Yun verfasserin aut Moody, D Branch verfasserin aut Janssens, Sophie verfasserin aut Drennan, Michael verfasserin aut Elewaut, Dirk verfasserin (orcid)0000-0003-3979-4824 aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 21(2020), 6 vom: 03. Mai (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:21 year:2020 number:6 day:03 month:05 https://dx.doi.org/10.15252/embr.201948927 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4315 GBV_ILN_4317 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 21 2020 6 03 05 |
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10.15252/embr.201948927 doi (DE-627)SPR058177426 (SPR)embr.201948927-e DE-627 ger DE-627 rakwb eng Govindarajan, Srinath verfasserin aut ER stress in antigen‐presenting cells promotes NKT cell activation through endogenous neutral lipids 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2020 Abstract CD1d‐restricted invariant natural killer T (iNKT) cells constitute a common glycolipid‐reactive innate‐like T‐cell subset with a broad impact on innate and adaptive immunity. While several microbial glycolipids are known to activate iNKT cells, the cellular mechanisms leading to endogenous CD1d‐dependent glycolipid responses remain largely unclear. Here, we show that endoplasmic reticulum (ER) stress in APCs is a potent inducer of CD1d‐dependent iNKT cell autoreactivity. This pathway relies on the presence of two transducers of the unfolded protein response: inositol‐requiring enzyme‐1a (IRE1α) and protein kinase R‐like ER kinase (PERK). Surprisingly, the neutral but not the polar lipids generated within APCs undergoing ER stress are capable of activating iNKT cells. These data reveal that ER stress is an important mechanism to elicit endogenous CD1d‐restricted iNKT cell responses through induction of distinct classes of neutral lipids. Synopsis Upon ER stress immunogenic lipids are produced that activate NKT cells. Defining the conditions required to generate endogenous high immunogenic lipid antigens paves the way for the design of novel lipids with immunomodulatory function. ER stress triggers IRE1α/PERK pathways to restore cellular homeostasis by generating distinct neutral and polar lipids.Neutral lipid species generated under these conditions are enriched and loaded onto CD1d to activate iNKT cells.Cytokines produced by iNKT cells during ER stress serve to activate the innate and adaptive immune system.ER stress is an important mechanism to elicit endogenous CD1d‐restricted iNKT cell responses. Graphical Abstract Upon ER stress immunogenic lipids are produced that activate NKT cells. Defining the conditions required to generate endogenous high immunogenic lipid antigens paves the way for the design of novel lipids with immunomodulatory function. antigen‐presenting cells (dpeaa)DE-He213 ER stress (dpeaa)DE-He213 lipid antigens (dpeaa)DE-He213 neutral lipid (dpeaa)DE-He213 NKT cells (dpeaa)DE-He213 Verheugen, Eveline verfasserin aut Venken, Koen verfasserin aut Gaublomme, Djoere verfasserin aut Maelegheer, Margaux verfasserin aut Cloots, Eva verfasserin aut Gysens, Fien verfasserin aut De Geest, Bruno G verfasserin aut Cheng, Tan‐Yun verfasserin aut Moody, D Branch verfasserin aut Janssens, Sophie verfasserin aut Drennan, Michael verfasserin aut Elewaut, Dirk verfasserin (orcid)0000-0003-3979-4824 aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 21(2020), 6 vom: 03. Mai (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:21 year:2020 number:6 day:03 month:05 https://dx.doi.org/10.15252/embr.201948927 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4315 GBV_ILN_4317 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 21 2020 6 03 05 |
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10.15252/embr.201948927 doi (DE-627)SPR058177426 (SPR)embr.201948927-e DE-627 ger DE-627 rakwb eng Govindarajan, Srinath verfasserin aut ER stress in antigen‐presenting cells promotes NKT cell activation through endogenous neutral lipids 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2020 Abstract CD1d‐restricted invariant natural killer T (iNKT) cells constitute a common glycolipid‐reactive innate‐like T‐cell subset with a broad impact on innate and adaptive immunity. While several microbial glycolipids are known to activate iNKT cells, the cellular mechanisms leading to endogenous CD1d‐dependent glycolipid responses remain largely unclear. Here, we show that endoplasmic reticulum (ER) stress in APCs is a potent inducer of CD1d‐dependent iNKT cell autoreactivity. This pathway relies on the presence of two transducers of the unfolded protein response: inositol‐requiring enzyme‐1a (IRE1α) and protein kinase R‐like ER kinase (PERK). Surprisingly, the neutral but not the polar lipids generated within APCs undergoing ER stress are capable of activating iNKT cells. These data reveal that ER stress is an important mechanism to elicit endogenous CD1d‐restricted iNKT cell responses through induction of distinct classes of neutral lipids. Synopsis Upon ER stress immunogenic lipids are produced that activate NKT cells. Defining the conditions required to generate endogenous high immunogenic lipid antigens paves the way for the design of novel lipids with immunomodulatory function. ER stress triggers IRE1α/PERK pathways to restore cellular homeostasis by generating distinct neutral and polar lipids.Neutral lipid species generated under these conditions are enriched and loaded onto CD1d to activate iNKT cells.Cytokines produced by iNKT cells during ER stress serve to activate the innate and adaptive immune system.ER stress is an important mechanism to elicit endogenous CD1d‐restricted iNKT cell responses. Graphical Abstract Upon ER stress immunogenic lipids are produced that activate NKT cells. Defining the conditions required to generate endogenous high immunogenic lipid antigens paves the way for the design of novel lipids with immunomodulatory function. antigen‐presenting cells (dpeaa)DE-He213 ER stress (dpeaa)DE-He213 lipid antigens (dpeaa)DE-He213 neutral lipid (dpeaa)DE-He213 NKT cells (dpeaa)DE-He213 Verheugen, Eveline verfasserin aut Venken, Koen verfasserin aut Gaublomme, Djoere verfasserin aut Maelegheer, Margaux verfasserin aut Cloots, Eva verfasserin aut Gysens, Fien verfasserin aut De Geest, Bruno G verfasserin aut Cheng, Tan‐Yun verfasserin aut Moody, D Branch verfasserin aut Janssens, Sophie verfasserin aut Drennan, Michael verfasserin aut Elewaut, Dirk verfasserin (orcid)0000-0003-3979-4824 aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 21(2020), 6 vom: 03. Mai (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:21 year:2020 number:6 day:03 month:05 https://dx.doi.org/10.15252/embr.201948927 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4315 GBV_ILN_4317 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 21 2020 6 03 05 |
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Govindarajan, Srinath @@aut@@ Verheugen, Eveline @@aut@@ Venken, Koen @@aut@@ Gaublomme, Djoere @@aut@@ Maelegheer, Margaux @@aut@@ Cloots, Eva @@aut@@ Gysens, Fien @@aut@@ De Geest, Bruno G @@aut@@ Cheng, Tan‐Yun @@aut@@ Moody, D Branch @@aut@@ Janssens, Sophie @@aut@@ Drennan, Michael @@aut@@ Elewaut, Dirk @@aut@@ |
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2020-05-03T00:00:00Z |
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Govindarajan, Srinath |
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Govindarajan, Srinath misc antigen‐presenting cells misc ER stress misc lipid antigens misc neutral lipid misc NKT cells ER stress in antigen‐presenting cells promotes NKT cell activation through endogenous neutral lipids |
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ER stress in antigen‐presenting cells promotes NKT cell activation through endogenous neutral lipids antigen‐presenting cells (dpeaa)DE-He213 ER stress (dpeaa)DE-He213 lipid antigens (dpeaa)DE-He213 neutral lipid (dpeaa)DE-He213 NKT cells (dpeaa)DE-He213 |
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ER stress in antigen‐presenting cells promotes NKT cell activation through endogenous neutral lipids |
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(DE-627)SPR058177426 (SPR)embr.201948927-e |
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ER stress in antigen‐presenting cells promotes NKT cell activation through endogenous neutral lipids |
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Govindarajan, Srinath |
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Govindarajan, Srinath Verheugen, Eveline Venken, Koen Gaublomme, Djoere Maelegheer, Margaux Cloots, Eva Gysens, Fien De Geest, Bruno G Cheng, Tan‐Yun Moody, D Branch Janssens, Sophie Drennan, Michael Elewaut, Dirk |
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Govindarajan, Srinath |
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10.15252/embr.201948927 |
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er stress in antigen‐presenting cells promotes nkt cell activation through endogenous neutral lipids |
| title_auth |
ER stress in antigen‐presenting cells promotes NKT cell activation through endogenous neutral lipids |
| abstract |
Abstract CD1d‐restricted invariant natural killer T (iNKT) cells constitute a common glycolipid‐reactive innate‐like T‐cell subset with a broad impact on innate and adaptive immunity. While several microbial glycolipids are known to activate iNKT cells, the cellular mechanisms leading to endogenous CD1d‐dependent glycolipid responses remain largely unclear. Here, we show that endoplasmic reticulum (ER) stress in APCs is a potent inducer of CD1d‐dependent iNKT cell autoreactivity. This pathway relies on the presence of two transducers of the unfolded protein response: inositol‐requiring enzyme‐1a (IRE1α) and protein kinase R‐like ER kinase (PERK). Surprisingly, the neutral but not the polar lipids generated within APCs undergoing ER stress are capable of activating iNKT cells. These data reveal that ER stress is an important mechanism to elicit endogenous CD1d‐restricted iNKT cell responses through induction of distinct classes of neutral lipids. Synopsis Upon ER stress immunogenic lipids are produced that activate NKT cells. Defining the conditions required to generate endogenous high immunogenic lipid antigens paves the way for the design of novel lipids with immunomodulatory function. ER stress triggers IRE1α/PERK pathways to restore cellular homeostasis by generating distinct neutral and polar lipids.Neutral lipid species generated under these conditions are enriched and loaded onto CD1d to activate iNKT cells.Cytokines produced by iNKT cells during ER stress serve to activate the innate and adaptive immune system.ER stress is an important mechanism to elicit endogenous CD1d‐restricted iNKT cell responses. Graphical Abstract Upon ER stress immunogenic lipids are produced that activate NKT cells. Defining the conditions required to generate endogenous high immunogenic lipid antigens paves the way for the design of novel lipids with immunomodulatory function. © The Author(s) 2020 |
| abstractGer |
Abstract CD1d‐restricted invariant natural killer T (iNKT) cells constitute a common glycolipid‐reactive innate‐like T‐cell subset with a broad impact on innate and adaptive immunity. While several microbial glycolipids are known to activate iNKT cells, the cellular mechanisms leading to endogenous CD1d‐dependent glycolipid responses remain largely unclear. Here, we show that endoplasmic reticulum (ER) stress in APCs is a potent inducer of CD1d‐dependent iNKT cell autoreactivity. This pathway relies on the presence of two transducers of the unfolded protein response: inositol‐requiring enzyme‐1a (IRE1α) and protein kinase R‐like ER kinase (PERK). Surprisingly, the neutral but not the polar lipids generated within APCs undergoing ER stress are capable of activating iNKT cells. These data reveal that ER stress is an important mechanism to elicit endogenous CD1d‐restricted iNKT cell responses through induction of distinct classes of neutral lipids. Synopsis Upon ER stress immunogenic lipids are produced that activate NKT cells. Defining the conditions required to generate endogenous high immunogenic lipid antigens paves the way for the design of novel lipids with immunomodulatory function. ER stress triggers IRE1α/PERK pathways to restore cellular homeostasis by generating distinct neutral and polar lipids.Neutral lipid species generated under these conditions are enriched and loaded onto CD1d to activate iNKT cells.Cytokines produced by iNKT cells during ER stress serve to activate the innate and adaptive immune system.ER stress is an important mechanism to elicit endogenous CD1d‐restricted iNKT cell responses. Graphical Abstract Upon ER stress immunogenic lipids are produced that activate NKT cells. Defining the conditions required to generate endogenous high immunogenic lipid antigens paves the way for the design of novel lipids with immunomodulatory function. © The Author(s) 2020 |
| abstract_unstemmed |
Abstract CD1d‐restricted invariant natural killer T (iNKT) cells constitute a common glycolipid‐reactive innate‐like T‐cell subset with a broad impact on innate and adaptive immunity. While several microbial glycolipids are known to activate iNKT cells, the cellular mechanisms leading to endogenous CD1d‐dependent glycolipid responses remain largely unclear. Here, we show that endoplasmic reticulum (ER) stress in APCs is a potent inducer of CD1d‐dependent iNKT cell autoreactivity. This pathway relies on the presence of two transducers of the unfolded protein response: inositol‐requiring enzyme‐1a (IRE1α) and protein kinase R‐like ER kinase (PERK). Surprisingly, the neutral but not the polar lipids generated within APCs undergoing ER stress are capable of activating iNKT cells. These data reveal that ER stress is an important mechanism to elicit endogenous CD1d‐restricted iNKT cell responses through induction of distinct classes of neutral lipids. Synopsis Upon ER stress immunogenic lipids are produced that activate NKT cells. Defining the conditions required to generate endogenous high immunogenic lipid antigens paves the way for the design of novel lipids with immunomodulatory function. ER stress triggers IRE1α/PERK pathways to restore cellular homeostasis by generating distinct neutral and polar lipids.Neutral lipid species generated under these conditions are enriched and loaded onto CD1d to activate iNKT cells.Cytokines produced by iNKT cells during ER stress serve to activate the innate and adaptive immune system.ER stress is an important mechanism to elicit endogenous CD1d‐restricted iNKT cell responses. Graphical Abstract Upon ER stress immunogenic lipids are produced that activate NKT cells. Defining the conditions required to generate endogenous high immunogenic lipid antigens paves the way for the design of novel lipids with immunomodulatory function. © The Author(s) 2020 |
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ER stress in antigen‐presenting cells promotes NKT cell activation through endogenous neutral lipids |
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Verheugen, Eveline Venken, Koen Gaublomme, Djoere Maelegheer, Margaux Cloots, Eva Gysens, Fien De Geest, Bruno G Cheng, Tan‐Yun Moody, D Branch Janssens, Sophie Drennan, Michael Elewaut, Dirk |
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While several microbial glycolipids are known to activate iNKT cells, the cellular mechanisms leading to endogenous CD1d‐dependent glycolipid responses remain largely unclear. Here, we show that endoplasmic reticulum (ER) stress in APCs is a potent inducer of CD1d‐dependent iNKT cell autoreactivity. This pathway relies on the presence of two transducers of the unfolded protein response: inositol‐requiring enzyme‐1a (IRE1α) and protein kinase R‐like ER kinase (PERK). Surprisingly, the neutral but not the polar lipids generated within APCs undergoing ER stress are capable of activating iNKT cells. These data reveal that ER stress is an important mechanism to elicit endogenous CD1d‐restricted iNKT cell responses through induction of distinct classes of neutral lipids.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Synopsis Upon ER stress immunogenic lipids are produced that activate NKT cells. 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