Hanuscheck, Nicholas ORCID: 0000-0003-1166-6273, Thalman, Carine ORCID: 0000-0001-7147-1887, Domingues, Micaela, Schmaul, Samantha ORCID: 0000-0001-5101-8508, Muthuraman, Muthuraman, Hetsch, Florian, Ecker, Manuela, Endle, Heiko ORCID: 0000-0002-1012-4563, Oshaghi, Mohammadsaleh, Martino, Gianvito, Kuhlmann, Tanja, Bozek, Katarzyna, van Beers, Tim ORCID: 0000-0002-5645-2853, Bittner, Stefan ORCID: 0000-0003-2179-3655, von Engelhardt, Jakob, Vogt, Johannes, Vogelaar, Christina Francisca and Zipp, Frauke (2022). Interleukin-4 receptor signaling modulates neuronal network activity. J. Exp. Med., 219 (6). NEW YORK: ROCKEFELLER UNIV PRESS. ISSN 1540-9538

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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-4R alpha) signaling pathway in synaptic processes, as indicated by transcriptome analysis in IL-4R alpha-deficient mice and human neurons with/without IL-4 treatment. Moreover, IL-4R alpha 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-4R alpha-deficient neurons. Acute effects of IL-4 treatment on postsynaptic currents in wild-type neurons were mediated via PKC gamma signaling release and led to increased inhibitory activity supporting the findings in IL-4R alpha-deficient neurons. In fact, the deficiency of IL-4R alpha 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-4R alpha and its presynaptic prevalence appear relevant for maintaining homeostasis of CNS synaptic function.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Hanuscheck, NicholasUNSPECIFIEDorcid.org/0000-0003-1166-6273UNSPECIFIED
Thalman, CarineUNSPECIFIEDorcid.org/0000-0001-7147-1887UNSPECIFIED
Domingues, MicaelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmaul, SamanthaUNSPECIFIEDorcid.org/0000-0001-5101-8508UNSPECIFIED
Muthuraman, MuthuramanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hetsch, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ecker, ManuelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Endle, HeikoUNSPECIFIEDorcid.org/0000-0002-1012-4563UNSPECIFIED
Oshaghi, MohammadsalehUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martino, GianvitoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuhlmann, TanjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bozek, KatarzynaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Beers, TimUNSPECIFIEDorcid.org/0000-0002-5645-2853UNSPECIFIED
Bittner, StefanUNSPECIFIEDorcid.org/0000-0003-2179-3655UNSPECIFIED
von Engelhardt, JakobUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vogt, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vogelaar, Christina FranciscaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zipp, FraukeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-683558
DOI: 10.1084/jem.20211887
Journal or Publication Title: J. Exp. Med.
Volume: 219
Number: 6
Date: 2022
Publisher: ROCKEFELLER UNIV PRESS
Place of Publication: NEW YORK
ISSN: 1540-9538
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
T-CELLS; INHIBITORY PLASTICITY; MULTIPLE-SCLEROSIS; MOUSE MODELS; VESICLE POOL; BRAIN; IL-4; MICROGLIA; RECOVERY; INFLAMMATIONMultiple languages
Immunology; Medicine, Research & ExperimentalMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/68355

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