# Roles of the integrated stress response in regulation of inflammatory reactions

**Authors:** Fan Jiang, Guei-Sheung Liu, Junjun Liu, Xiaopei Cui, Yanqiu Xing

PMC · DOI: 10.3389/fimmu.2026.1747401 · 2026-02-25

## TL;DR

This paper reviews how the integrated stress response may help reduce inflammation and could be a target for new therapies.

## Contribution

It compiles experimental evidence showing the anti-inflammatory potential of the integrated stress response.

## Key findings

- ISR activation leads to reduced protein synthesis and may suppress inflammation.
- In vitro and in vivo studies support the anti-inflammatory role of ISR.
- ISR is proposed as a potential target for developing anti-inflammatory drugs.

## Abstract

The integrated stress response (ISR) is a conserved cyto-protective mechanism, which has fundamental roles in maintaining cell viability under various conditions when intracellular and/or extracellular homeostasis is disrupted. ISR features phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2α), leading to a global reduction in protein synthesis. Emerging evidence suggests that activation of ISR may have anti-inflammatory effects. In this concise review, we summarize the current experimental evidence in this regard from both in vitro and in vivo studies. It is suggested that ISR may represent a potential drug target for developing novel anti-inflammatory therapies.

## Linked entities

- **Genes:** EIF2A (eukaryotic translation initiation factor 2A) [NCBI Gene 83939]

## Full-text entities

- **Genes:** EIF2A (eukaryotic translation initiation factor 2A) [NCBI Gene 83939] {aka CDA02, EIF-2A, MST089, MSTP004, MSTP089}
- **Diseases:** inflammatory (MESH:D007249)

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12975573/full.md

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Source: https://tomesphere.com/paper/PMC12975573