Figure 4.

ER stress/UPR: effects on innate immunity. ER stress starts with the accumulation of unfolded proteins in the lumen of the ER. It activates a UPR via engagement of 3 UPR sensors and their respective signaling cascades: PERK‐EIF2α‐ATF4, ATF6, and IRE1α‐XBP‐1 pathways. These 3 UPR pathways lead to a global inhibition of protein translation and to expression of UPR target genes that are involved in the resolution of ER stress via protein folding processes or ER‐associated degradation of unfolded proteins (ERAD). ER stress/UPR was proposed to activate different immune signaling cascades, of note downstream of TLRs, such as JNK, NF‐κB, and IRF3 pathways, and, therefore, to promote the production of inflammatory cytokines. ER stress/UPR also activates NOD1/2‐dependent inflammatory cytokine production.