IL-37 expression reduces acute and chronic neuroinflammation and rescues cognitive impairment in an Alzheimer's disease mouse model
- Technische Universität Braunschweig, Germany
- Helmholtz Centre for Infection Research, Germany
- University of Colorado Health, United States
Abstract
The anti-inflammatory cytokine interleukin-37 (IL-37) belongs to the IL-1 family but is not expressed in mice. We used a human IL‑37 (hIL-37tg) expressing mouse, which has been subjected to various models of local and systemic inflammation as well as immunological challenges. Previous studies reveal an immunomodulatory role of IL-37, which can be characterized as an important suppressor of innate immunity. Here, we examined the functions of IL-37 in the central nervous system and explored the effects of IL-37 on neuronal architecture and function, microglial phenotype, cytokine production and behavior after inflammatory challenge by intraperitoneal LPS-injection. In wild-type mice, decreased spine density, activated microglial phenotype and impaired long-term potentiation (LTP) were observed after LPS injection, whereas hIL-37tg mice showed no impairment. In addition, we crossed the hIL-37tg mouse with an animal model of Alzheimer's disease (APP/PS1) to investigate the anti-inflammatory properties of IL-37 under chronic neuroinflammatory conditions. Our results show that expression of IL-37 is able to limit inflammation in the brain after acute inflammatory events and prevent loss of cognitive abilities in a mouse model of AD.
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All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for all Figures.
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Funding
Deutsche Forschungsgemeinschaft (SFB854)
- Martin Korte
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experimental procedures and protocolls were authorized by the animal welfare representative of the TU Braunschweig and the LAVES of the state of Lower Saxony in Germany (Oldenburg, Germany) (33.19-42502-04-16/2170).
Copyright
© 2022, Lonnemann et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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IL-37 expression reduces acute and chronic neuroinflammation and rescues cognitive impairment in an Alzheimer's disease mouse model
eLife 11:e75889.
https://doi.org/10.7554/eLife.75889
