PerspectiveSignaling

Integrating stress responses and immunity

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Science  05 Jul 2019:
Vol. 365, Issue 6448, pp. 28-29
DOI: 10.1126/science.aay0987

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Summary

The integrated stress response (ISR) is a gene expression program that protects cells from amino acid deprivation, oxidative stress, or stress in the endoplasmic reticulum (ER) that is caused by protein misfolding and aggregation (1). Phosphorylation of the eukaryotic initiation factor 2α (eIF2α) initiates the ISR, but it also has a role in innate immunity (2, 3). In particular, eIF2α is important to harness the full capacity of different immune cells to produce inflammatory cytokines or type-I interferon in response to microbial cues. On page 47 of this issue, Abdel-Nour et al. (4) reveal that in response to bacterial infection, the ISR promotes expression of heat shock protein family B-member 8 (HSPB8), which controls the assembly of signaling hubs for inflammatory cytokine production. This involves the formation of amyloid fibrils, which are also associated with neuroinflammation and neurodegeneration. Thus, understanding these regulatory processes may reveal new targets for the prevention of inflammation.

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