Elevated IL-22 as a result of stress-induced gut leakage suppresses septal neuron activation to ameliorate anxiety-like behavior
Psychological stress and its sequelae pose a major challenge to public health. Immune activation is conventionally thought to aggravate stress-related mental diseases such as anxiety disorders and depression. Here, we sought to identify potentially beneficial consequences of immune activation in response to stress. We showed that stress led to increased interleukin (IL)-22 production in the intestine as a result of stress-induced gut leakage. IL-22 was both necessary and sufficient to attenuate stress-induced anxiety behaviors in mice. More specifically, IL-22 gained access to the septal area of the brain and directly suppressed neuron activation. Furthermore, human patients with clinical depression displayed reduced IL-22 levels, and exogenous IL-22 treatment ameliorated depressive-like behavior elicited by chronic stress in mice. Our study thus identifies a gut-brain axis in response to stress, whereby IL-22 reduces neuronal activation and concomitant anxiety behavior, suggesting that early immune activation can provide protection against psychological stress.
Authors
- Xinyu Zhou (ORCID: https://orcid.org/0000-0003-1908-0357)
- Boxun Lu (ORCID: https://orcid.org/0000-0002-1675-9340)
- Anoj Ilanges (ORCID: https://orcid.org/0000-0003-2611-6768)
- Zheyu Jin (ORCID: https://orcid.org/0000-0002-8006-8974)
- Xueer Liu
- Marc Schneeberger (ORCID: https://orcid.org/0000-0001-7369-104X)
- Jixi Li (ORCID: https://orcid.org/0000-0003-3463-3175)
- Rani Shiao
- Qingqing Qi (ORCID: https://orcid.org/0009-0008-2514-4613)
- Changchun Wang (ORCID: https://orcid.org/0000-0003-3183-2160)
- Xiaofei Yu (ORCID: https://orcid.org/0000-0002-1712-331X)
- Hongyan Wu (ORCID: https://orcid.org/0000-0002-6887-2548)
- Mengyu Xia
- Lei Chen (ORCID: https://orcid.org/0000-0001-7864-8649)
- Teng Teng (ORCID: https://orcid.org/0000-0003-3701-0002)
- Yi Han (ORCID: https://orcid.org/0000-0002-3941-9998)
- J. Lan (ORCID: https://orcid.org/0009-0006-4423-2403)
- Hongbin Sun (ORCID: https://orcid.org/0000-0003-2118-0947)
- Junmei Lü (ORCID: https://orcid.org/0000-0002-8592-0556)
- Wei Shen
- Jie Wang (ORCID: https://orcid.org/0000-0002-2997-3450)
Institutions
- Howard Hughes Medical Institute (US)
- Janelia Research Campus (US)
- Fudan University (CN)
- Renji Hospital (CN)
- ShanghaiTech University (CN)
- Yale University (US)
- The Affiliated Yongchuan Hospital of Chongqing Medical University (CN)
- Rockefeller University (US)
- Chongqing Medical University (CN)
Publication Details
- Journal
- Immunity
- Published
- 2024-12-06
- DOI
- https://doi.org/10.1016/j.immuni.2024.11.008
- Citations
- 22
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 5.14
Funders
- Howard Hughes Medical Institute
- Helen Hay Whitney Foundation
- National Natural Science Foundation of China
- Science and Technology Commission of Shanghai Municipality
- National Key Research and Development Program of China
- National Key Research and Development Program of China Stem Cell and Translational Research