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ER stress in antigen‐presenting cells promotes NKT cell activation through endogenous neutral lipids

Srinath Govindarajan (UGent) , Eveline Verheugen (UGent) , Koen Venken (UGent) , Djoere Gaublomme (UGent) , Margaux Maelegheer (UGent) , Eva Cloots (UGent) , Fien Gysens (UGent) , Bruno De Geest (UGent) , Tan‐Yun Cheng, D Branch Moody, et al.
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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.
Keywords
Genetics, Biochemistry, Molecular Biology

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MLA
Govindarajan, Srinath, et al. “ER Stress in Antigen‐presenting Cells Promotes NKT Cell Activation through Endogenous Neutral Lipids.” EMBO REPORTS, 2020.
APA
Govindarajan, S., Verheugen, E., Venken, K., Gaublomme, D., Maelegheer, M., Cloots, E., … Elewaut, D. (2020). ER stress in antigen‐presenting cells promotes NKT cell activation through endogenous neutral lipids. EMBO REPORTS.
Chicago author-date
Govindarajan, Srinath, Eveline Verheugen, Koen Venken, Djoere Gaublomme, Margaux Maelegheer, Eva Cloots, Fien Gysens, et al. 2020. “ER Stress in Antigen‐presenting Cells Promotes NKT Cell Activation through Endogenous Neutral Lipids.” EMBO REPORTS.
Chicago author-date (all authors)
Govindarajan, Srinath, Eveline Verheugen, Koen Venken, Djoere Gaublomme, Margaux Maelegheer, Eva Cloots, Fien Gysens, Bruno De Geest, Tan‐Yun Cheng, D Branch Moody, Sophie Janssens, Michael Drennan, and Dirk Elewaut. 2020. “ER Stress in Antigen‐presenting Cells Promotes NKT Cell Activation through Endogenous Neutral Lipids.” EMBO REPORTS.
Vancouver
1.
Govindarajan S, Verheugen E, Venken K, Gaublomme D, Maelegheer M, Cloots E, et al. ER stress in antigen‐presenting cells promotes NKT cell activation through endogenous neutral lipids. EMBO REPORTS. 2020;
IEEE
[1]
S. Govindarajan et al., “ER stress in antigen‐presenting cells promotes NKT cell activation through endogenous neutral lipids,” EMBO REPORTS, 2020.
@article{8660969,
  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.},
  articleno    = {e48927},
  author       = {Govindarajan, Srinath and Verheugen, Eveline and Venken, Koen and Gaublomme, Djoere and Maelegheer, Margaux and Cloots, Eva and Gysens, Fien and De Geest, Bruno and Cheng, Tan‐Yun and Moody, D Branch and Janssens, Sophie and Drennan, Michael and Elewaut, Dirk},
  issn         = {1469-221X},
  journal      = {EMBO REPORTS},
  keywords     = {Genetics,Biochemistry,Molecular Biology},
  language     = {eng},
  pages        = {14},
  title        = {ER stress in antigen‐presenting cells promotes NKT cell activation through endogenous neutral lipids},
  url          = {http://dx.doi.org/10.15252/embr.201948927},
  year         = {2020},
}

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