Interleukin-13 and its receptor are synaptic proteins involved in plasticity and neuroprotection
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Interleukin-13 and its receptor are synaptic proteins involved in plasticity and neuroprotection. / Li, Shun; Olde Heuvel, Florian; Rehman, Rida; Aousji, Oumayma; Froehlich, Albrecht; Li, Zhenghui; Jark, Rebecca; Zhang, Wanhong; Conquest, Alison; Woelfle, Sarah; Schoen, Michael; O Meara, Caitlin C; Reinhardt, Richard Lee; Voehringer, David; Kassubek, Jan; Ludolph, Albert; Huber-Lang, Markus; Knöll, Bernd; Morganti-Kossmann, Maria Cristina; Brockmann, Marisa M; Boeckers, Tobias; Roselli, Francesco.
in: NAT COMMUN, Jahrgang 14, Nr. 1, 200, 13.01.2023.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Interleukin-13 and its receptor are synaptic proteins involved in plasticity and neuroprotection
AU - Li, Shun
AU - Olde Heuvel, Florian
AU - Rehman, Rida
AU - Aousji, Oumayma
AU - Froehlich, Albrecht
AU - Li, Zhenghui
AU - Jark, Rebecca
AU - Zhang, Wanhong
AU - Conquest, Alison
AU - Woelfle, Sarah
AU - Schoen, Michael
AU - O Meara, Caitlin C
AU - Reinhardt, Richard Lee
AU - Voehringer, David
AU - Kassubek, Jan
AU - Ludolph, Albert
AU - Huber-Lang, Markus
AU - Knöll, Bernd
AU - Morganti-Kossmann, Maria Cristina
AU - Brockmann, Marisa M
AU - Boeckers, Tobias
AU - Roselli, Francesco
N1 - © 2023. The Author(s).
PY - 2023/1/13
Y1 - 2023/1/13
N2 - 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.
AB - 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.
KW - Animals
KW - Humans
KW - Male
KW - Mice
KW - Rats
KW - Brain Injuries, Traumatic/genetics
KW - Interleukin-13/genetics
KW - Neuronal Plasticity/physiology
KW - Neurons/metabolism
KW - Neuroprotection
U2 - 10.1038/s41467-023-35806-8
DO - 10.1038/s41467-023-35806-8
M3 - SCORING: Journal article
C2 - 36639371
VL - 14
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
IS - 1
M1 - 200
ER -