Premium
ER stress in antigen‐presenting cells promotes NKT cell activation through endogenous neutral lipids
Author(s) -
Govindarajan Srinath,
Verheugen Eveline,
Venken Koen,
Gaublomme Djoere,
Maelegheer Margaux,
Cloots Eva,
Gysens Fien,
De Geest Bruno G,
Cheng TanYun,
Moody D Branch,
Janssens Sophie,
Drennan Michael,
Elewaut Dirk
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201948927
Subject(s) - inflammation , medicine , immunology
CD 1d‐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 CD 1d‐dependent glycolipid responses remain largely unclear. Here, we show that endoplasmic reticulum ( ER ) stress in APC s is a potent inducer of CD 1d‐dependent iNKT cell autoreactivity. This pathway relies on the presence of two transducers of the unfolded protein response: inositol‐requiring enzyme‐1a ( IRE 1α) and protein kinase R‐like ER kinase ( PERK ). Surprisingly, the neutral but not the polar lipids generated within APC s undergoing ER stress are capable of activating iNKT cells. These data reveal that ER stress is an important mechanism to elicit endogenous CD 1d‐restricted iNKT cell responses through induction of distinct classes of neutral lipids.