Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Highlight
  • Published:

Neuroimmunology

IL-22 protects against stress-induced anxiety

Nature Reviews Immunology volume 25, page 75 (2025)Cite this article

Subjects

Despite the prevailing view that immune activation exacerbates stress-related psychological conditions, Mengyu Xia et al. speculated that stress-induced immune activation may have some benefits given its evolutionary conservation. Reporting in Immunity, they now show that stress-induced gut leakage and immune activation lead to the release of IL-22, which acts on septal neurons in the brain to dampen their activation and reduce concomitant anxiety behaviour.

To model mildly stressful conditions, mice were restrained for 30 minutes each day for 3 days. This was sufficient to increase gut permeability and cause immune activation, as indicated by activation of intestinal NF-κB and altered peripheral cytokine profiles. In particular, higher IL-22 levels were observed in stressed mice than in resting mice. Studies using reporter mice showed that the IL-22 increase was primarily derived from expanded populations of T helper 17 (TH17) cells. TH17 cell expansion was stimulated by microbiota-derived signals that drove an increase in circulating IL-1β. Accordingly, depletion of the microbiota with antibiotics prevented the stress-induced increase in IL-1β and IL-22-producing TH17 cells.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

References

Original article

Download references

Author information

Authors and Affiliations

  1. Nature Reviews Immunology http://www.nature.com/nri/

    Lucy Bird

Authors
  1. Lucy Bird
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Lucy Bird.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bird, L. IL-22 protects against stress-induced anxiety. Nat Rev Immunol 25, 75 (2025). https://doi.org/10.1038/s41577-024-01127-0

Download citation

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41577-024-01127-0

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing