IL-37 expression reduces acute and chronic neuroinflammation and rescues cognitive impairment in an Alzheimer's disease mouse model

  1. Niklas Lonnemann
  2. Shirin Hosseini
  3. Melanie Ohm
  4. Robert Geffers
  5. Karsten Hiller
  6. Charles A Dinarello  Is a corresponding author
  7. Martin Korte  Is a corresponding author
  1. Technische Universität Braunschweig, Germany
  2. Helmholtz Centre for Infection Research, Germany
  3. 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.

Data availability

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.

Article and author information

Author details

  1. Niklas Lonnemann

    Department of Cellular Neurobiology, Technische Universität Braunschweig, Braunschweig, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Shirin Hosseini

    Department of Cellular Neurobiology, Technische Universität Braunschweig, Braunschweig, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Melanie Ohm

    Department of Cellular Neurobiology, Technische Universität Braunschweig, Braunschweig, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Robert Geffers

    Genome Analytics Group, Helmholtz Centre for Infection Research, Braunschweig, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Karsten Hiller

    Braunschweig Integrated Centre of Systems Biology, Technische Universität Braunschweig, Braunschweig, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Charles A Dinarello

    Department of Medicine, University of Colorado Health, Aurora, United States
    For correspondence
    dinare333@aol.com
    Competing interests
    The authors declare that no competing interests exist.
  7. Martin Korte

    Department of Cellular Neurobiology, Technische Universität Braunschweig, Braunschweig, Germany
    For correspondence
    m.korte@tu-bs.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6956-5913

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.

Reviewing Editor

  1. Xiaoyu Hu, Tsinghua University, China

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).

Version history

  1. Preprint posted: November 26, 2021 (view preprint)
  2. Received: November 26, 2021
  3. Accepted: August 29, 2022
  4. Accepted Manuscript published: August 30, 2022 (version 1)
  5. Version of Record published: September 16, 2022 (version 2)

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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  1. Niklas Lonnemann
  2. Shirin Hosseini
  3. Melanie Ohm
  4. Robert Geffers
  5. Karsten Hiller
  6. Charles A Dinarello
  7. Martin Korte
(2022)
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

Share this article

https://doi.org/10.7554/eLife.75889

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