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.

Interleukin-4 receptor signaling modulates neuronal network activity / Hanuscheck, N.; Thalman, C.; Domingues, M.; Schmaul, S.; Muthuraman, M.; Hetsch, F.; Ecker, M.; Endle, H.; Oshaghi, M.; Martino, G.; Kuhlmann, T.; Bozek, K.; Beers, T.; Bittner, S.; Engelhardt, J. V.; Vogt, J.; Vogelaar, C. F.; Zipp, F.. - In: JOURNAL OF EXPERIMENTAL MEDICINE. - ISSN 0022-1007. - 219:6(2022). [10.1084/jem.20211887]

Interleukin-4 receptor signaling modulates neuronal network activity

Martino G.;
2022-01-01

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.
2022
T-CELLS, INHIBITORY PLASTICITY, MULTIPLE-SCLEROSIS, MOUSE MODELS, VESICLE POOL, BRAIN, IL-4, MICROGLIA, RECOVERY, INFLAMMATION
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/145636
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