Emerging functions of the unfolded protein response in immunity

Nat Immunol. 2014 Oct;15(10):910-9. doi: 10.1038/ni.2991.


The unfolded protein response (UPR) has traditionally been viewed as an adaptive response triggered by the accumulation of unfolded proteins in the endoplasmic reticulum (ER) and aimed at restoring ER function. The UPR can also be an anticipatory response that is activated well before the disruption of protein homeostasis. UPR signaling intersects at many levels with the innate and adaptive immune responses. In some types of cells of the immune system, such as dendritic cells (DCs) and B cells, particular sensors that detect the UPR seem to be constitutively active in the absence of induction of the traditional UPR gene program and are necessary for antigen presentation and immunoglobulin synthesis. The UPR also influences signaling via Toll-like receptors (TLRs) and activation of the transcription factor NF-κB, and some pathogens subvert the UPR. This Review summarizes these emerging noncanonical functions of the UPR in immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptive Immunity / immunology*
  • Animals
  • Humans
  • Immune System / cytology
  • Immune System / metabolism
  • Immunity, Innate / immunology*
  • Models, Immunological
  • NF-kappa B / immunology
  • NF-kappa B / metabolism
  • Signal Transduction / immunology*
  • Toll-Like Receptors / immunology
  • Toll-Like Receptors / metabolism
  • Unfolded Protein Response / immunology*


  • NF-kappa B
  • Toll-Like Receptors