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

Shun, L.; olde Heuvel, F.; Rehman, R.; Li, Z.; Aousji, O.; Froehlich, A.; Zhang, W.; Conquest, A.; Woelfle, S.; Schoen, M.; O Meara, C.; Reinhardt, R. L.; Voehringer, D.; Kassubek, J.; Ludolph, A.; Huber-Lang, M.; Knoell, B.; Morganti-Kossmann, M. C.; Boeckers, T. M.; Roselli, F.

doi:10.1101/2021.12.01.470746

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bioRxiv · 10.1101/2021.12.01.470746

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

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Abstract

Immune system molecules are expressed by neurons, often for unknown functions. 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 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 CSF. Thus, IL-13 is a previously unrecognized 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 a new entry point for interventions in the pathophysiology of TBI.

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Shun, L., olde Heuvel, F., Rehman, R., Li, Z., Aousji, O., Froehlich, A., Zhang, W., Conquest, A., Woelfle, S., Schoen, M., O Meara, C., Reinhardt, R. L., Voehringer, D., Kassubek, J., Ludolph, A., Huber-Lang, M., Knoell, B., Morganti-Kossmann, M. C., Boeckers, T. M., Roselli, F.. 2021-12-03. Interleukin-13 and its receptor are synaptic proteins involved in plasticity and neuroprotection. https://doi.org/10.1101/2021.12.01.470746

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