Endoplasmic reticulum stress in immunity

Annu Rev Immunol. 2015;33:107-38. doi: 10.1146/annurev-immunol-032414-112116. Epub 2014 Dec 10.


Immune responses occur in the midst of a variety of cellular stresses that can severely perturb endoplasmic reticulum (ER) function. The unfolded protein response is a three-pronged signaling axis dedicated to preserving ER homeostasis. In this review, we highlight many important and emerging functional roles for ER stress in immunity, focusing on how the bidirectional cross talk between immunological processes and basic cell biology leads to pleiotropic signaling outcomes and enhanced sensitivity to inflammatory stimuli. We also discuss how dysregulated ER stress responses can provoke many diseases, including autoimmunity, firmly positioning the unfolded protein response as a major therapeutic target in human disease.

Keywords: ATF6; IRE1; PERK; XBP-1; inflammation; proteostasis.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism
  • Autoimmunity
  • Cell Differentiation / immunology
  • Endoplasmic Reticulum / metabolism
  • Endoplasmic Reticulum Stress / immunology*
  • Humans
  • Immune System Phenomena
  • Immunity*
  • Infections / etiology
  • Infections / metabolism
  • Inflammation / immunology
  • Inflammation / metabolism
  • Protein Binding
  • Signal Transduction
  • Transcription Factors / metabolism
  • Unfolded Protein Response


  • Transcription Factors