| First Author | Hanuscheck N | Year | 2022 |
| Journal | J Exp Med | Volume | 219 |
| Issue | 6 | PubMed ID | 35587822 |
| Mgi Jnum | J:325138 | Mgi Id | MGI:7284042 |
| Doi | 10.1084/jem.20211887 | Citation | Hanuscheck N, et al. (2022) Interleukin-4 receptor signaling modulates neuronal network activity. J Exp Med 219(6):e20211887 |
| abstractText | 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-4Ralpha) signaling pathway in synaptic processes, as indicated by transcriptome analysis in IL-4Ralpha-deficient mice and human neurons with/without IL-4 treatment. Moreover, IL-4Ralpha 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-4Ralpha-deficient neurons. Acute effects of IL-4 treatment on postsynaptic currents in wild-type neurons were mediated via PKCgamma signaling release and led to increased inhibitory activity supporting the findings in IL-4Ralpha-deficient neurons. In fact, the deficiency of IL-4Ralpha 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-4Ralpha and its presynaptic prevalence appear relevant for maintaining homeostasis of CNS synaptic function. |
