Interleukin-13 and its receptor are synaptic proteins involved in plasticity and neuroprotection

Li S, olde Heuvel F, Rehman R, Aousji O, Froehlich A, Li Z, Jark R, Zhang W, Conquest A, Woelfle S, Schoen M, O´Meara CC, Reinhardt RL, Vöhringer D, Kassubek J, Ludolph A, Huber-Lang M, Knöll B, Morganti-Kossmann MC, Brockmann MM, Boeckers T, Roselli F (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 14

Article Number: 200

Journal Issue: 1

DOI: 10.1038/s41467-023-35806-8

Abstract

Immune system molecules are expressed by neurons, yet their functions are often unknown. We have identified IL-13 and its receptor IL-13Ra1 as neuronal, synaptic proteins in mouse, rat, and human brains, whose engagement upregulates the phosphorylation of NMDAR and AMPAR subunits and, in turn, increases synaptic activity and CREB-mediated transcription. We demonstrate that increased IL-13 is a hallmark of traumatic brain injury (TBI) in male mice as well as in two distinct cohorts of human patients. We also provide evidence that IL-13 upregulation protects neurons from excitotoxic death. We show IL-13 upregulation occurring in several cohorts of human brain samples and in cerebrospinal fluid (CSF). Thus, IL-13 is a physiological modulator of synaptic physiology of neuronal origin, with implications for the establishment of synaptic plasticity and the survival of neurons under injury conditions. Furthermore, we suggest that the neuroprotection afforded through the upregulation of IL-13 represents an entry point for interventions in the pathophysiology of TBI.

Authors with CRIS profile

David Vöhringer Professur für Infektionsabwehr und Toleranz

Involved external institutions

Universitätsklinikum Ulm DE Germany (DE) Universität Ulm DE Germany (DE) The Alfred Hospital AU Australia (AU) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Medical College of Wisconsin (MCW) US United States (USA) (US) University of Colorado Anschutz Medical Campus US United States (USA) (US)

How to cite

APA:

Li, S., olde Heuvel, F., Rehman, R., Aousji, O., Froehlich, A., Li, Z.,... Roselli, F. (2023). Interleukin-13 and its receptor are synaptic proteins involved in plasticity and neuroprotection. Nature Communications, 14(1). https://dx.doi.org/10.1038/s41467-023-35806-8

MLA:

Li, Shun, et al. "Interleukin-13 and its receptor are synaptic proteins involved in plasticity and neuroprotection." Nature Communications 14.1 (2023).

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