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

Shun Li, Florian olde Heuvel, Rida Rehman, Oumayma Aousji, Albrecht Froehlich, Zhenghui Li, Rebecca Jark, Wanhong Zhang, Alison Conquest, Sarah Woelfle, Michael Schoen, Caitlin C. O´Meara, Richard Lee Reinhardt, David Voehringer, Jan Kassubek, Albert Ludolph, Markus Huber-Lang, Bernd Knöll, Maria Cristina Morganti-Kossmann, Marisa M. Brockmann, Tobias Boeckers and Francesco Roselli ()
Additional contact information
Shun Li: Ulm University
Florian olde Heuvel: Ulm University
Rida Rehman: Ulm University
Oumayma Aousji: Ulm University
Albrecht Froehlich: Ulm University
Zhenghui Li: Ulm University
Rebecca Jark: University Medical Centre Hamburg-Eppendorf
Wanhong Zhang: Kaifeng central Hospital
Alison Conquest: TheAlfred Hospital
Sarah Woelfle: Ulm University
Michael Schoen: Ulm University
Caitlin C. O´Meara: Medical College of Wisconsin
Richard Lee Reinhardt: University of Colorado Medical School
David Voehringer: Friedrich-Alexander University Erlangen-Nuremberg (FAU)
Jan Kassubek: Ulm University
Albert Ludolph: Ulm University
Markus Huber-Lang: Ulm University
Bernd Knöll: Ulm University
Maria Cristina Morganti-Kossmann: TheAlfred Hospital
Marisa M. Brockmann: University Medical Centre Hamburg-Eppendorf
Tobias Boeckers: Ulm University
Francesco Roselli: Ulm University

Nature Communications, 2023, vol. 14, issue 1, 1-21

Abstract: 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.

Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-35806-8

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DOI: 10.1038/s41467-023-35806-8

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