Behavioral changes in mice lacking interleukin-33

Eisuke Dohi, Eric Y. Choi, Indigo V.L. Rose, Akiho S. Murata, Sharon Chow, Minae Niwa, Shin Ichi Kano

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Interleukin (IL)-33 is a member of the IL-1 family of cytokines. IL-33 is expressed in nuclei and secreted as alarmin upon cellular damage to deliver a danger signal to the surrounding cells. Previous studies showed that IL-33 is expressed in the brain and that it is involved in neuroinflammatory and neurodegenerative processes in both humans and rodents. Nevertheless, the role of IL-33 in physiological brain function and behavior remains unclear. Here, we have investigated the behaviors of mice lacking IL-33 (Il33-/- mice). IL-33 is constitutively expressed throughout the adult mouse brain, mainly in oligodendrocyte-lineage cells and astrocytes. Notably, Il33-/- mice exhibited reduced anxiety-like behaviors in the elevated plus maze (EPM) and the open field test (OFT), as well as deficits in social novelty recognition, despite their intact sociability, in the three-chamber social interaction test. The immunoreactivity of c-Fos proteins, an indicator of neuronal activity, was altered in several brain regions implicated in anxiety-related behaviors, such as the medial prefrontal cortex (mPFC), amygdala, and piriform cortex (PCX), in Il33-/- mice after the EPM. Altered c-Fos immunoreactivity in Il33-/-mice was not correlated with IL-33 expression in wild-type (WT) mice nor was IL-33 expression affected by the EPM in WT mice. Thus, our study has revealed that Il33-/- mice exhibit multiple behavioral deficits, such as reduced anxiety and impaired social recognition. Our findings also indicate that IL-33 may regulate the development and/or maturation of neuronal circuits, rather than control neuronal activities in adult brains.

Original languageEnglish (US)
Article numbere0147-17.2017
Issue number6
StatePublished - Nov 1 2017


  • Anxiety
  • Astrocytes
  • Cytokines
  • IL-33
  • Oligodendrocytes
  • Social behavior

ASJC Scopus subject areas

  • Neuroscience(all)


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