Interleukin-4 receptor signaling modulates neuronal network activity

J Exp Med. 2022 Jun 6;219(6):e20211887. doi: 10.1084/jem.20211887. Epub 2022 May 19.

Abstract

Evidence is emerging that immune responses not only play a part in the central nervous system (CNS) in diseases but may also be relevant for healthy conditions. We discovered a major role for the interleukin-4 (IL-4)/IL-4 receptor alpha (IL-4Rα) signaling pathway in synaptic processes, as indicated by transcriptome analysis in IL-4Rα-deficient mice and human neurons with/without IL-4 treatment. Moreover, IL-4Rα is expressed presynaptically, and locally available IL-4 regulates synaptic transmission. We found reduced synaptic vesicle pools, altered postsynaptic currents, and a higher excitatory drive in cortical networks of IL-4Rα-deficient neurons. Acute effects of IL-4 treatment on postsynaptic currents in wild-type neurons were mediated via PKCγ signaling release and led to increased inhibitory activity supporting the findings in IL-4Rα-deficient neurons. In fact, the deficiency of IL-4Rα resulted in increased network activity in vivo, accompanied by altered exploration and anxiety-related learning behavior; general learning and memory was unchanged. In conclusion, neuronal IL-4Rα and its presynaptic prevalence appear relevant for maintaining homeostasis of CNS synaptic function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Interleukin-4* / metabolism
  • Mice
  • Mice, Knockout
  • Neurons / metabolism
  • Receptors, Interleukin-4* / metabolism
  • Signal Transduction

Substances

  • Receptors, Interleukin-4
  • Interleukin-4