Interleukin-4 Receptor Signaling Modulates Neuronal Network Activity

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2022 May 19

PMID 35587822

Authors

Nicholas Hanuscheck

Carine Thalman

Micaela Domingues

Samantha Schmaul

Muthuraman Muthuraman

Florian Hetsch

Manuela Ecker

Heiko Endle

Mohammadsaleh Oshaghi

Gianvito Martino

Tanja Kuhlmann

Katarzyna Bozek

Tim van Beers

Stefan Bittner

Jakob von Engelhardt

Johannes Vogt

Christina Francisca Vogelaar

Frauke Zipp

Affiliations

Soon will be listed here.

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.

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