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

被引：42

作者：

Li, Shun ^{[1
]}

Heuvel, Florian Olde ^{[1
]}

Rehman, Rida ^{[1
]}

Aousji, Oumayma ^{[1
]}

Froehlich, Albrecht ^{[1
]}

Li, Zhenghui ^{[1
,2
]}

Jark, Rebecca ^{[3
]}

Zhang, Wanhong ^{[2
]}

Conquest, Alison ^{[4
,5
]}

Woelfle, Sarah ^{[6
]}

Schoen, Michael ^{[6
]}

O'Meara, Caitlin C. C. ^{[7
]}

Reinhardt, Richard Lee ^{[8
]}

Voehringer, David ^{[9
]}

Kassubek, Jan ^{[1
,10
]}

Ludolph, Albert ^{[1
,10
]}

Huber-Lang, Markus ^{[11
]}

Knoell, Bernd ^{[12
]}

Morganti-Kossmann, Maria Cristina ^{[4
,5
,13
]}

Brockmann, Marisa M. ^{[3
]}

Boeckers, Tobias ^{[6
,10
]}

Roselli, Francesco ^{[1
,10
]}

机构：

[1] Ulm Univ, Dept Neurol, Ulm, Germany

[2] Kaifeng Cent Hosp, Dept Neurosurg, Kaifeng, Peoples R China

[3] Univ Med Ctr Hamburg Eppendorf, Ctr Mol Neurobiol Hamburg, Hamburg, Germany

[4] TheAlfred Hosp, Natl Trauma Res Inst, Melbourne, Vic, Australia

[5] Alfred Hosp, Dept Neurosurg, Melbourne, Vic, Australia

[6] Ulm Univ, Inst Anat & Cell Biol, Ulm, Germany

[7] Med Coll Wisconsin, Cardiovasc Ctr, Milwaukee, WI USA

[8] Univ Colorado, Dept Immunol & Microbiol, Med Sch, Aurora, CO USA

[9] Friedrich Alexander Univ Erlangen Nuremberg FAU, Dept Infect Biol, Erlangen, Germany

[10] German Ctr Neurodegenerat Dis DZNE Ulm, Ulm, Germany

[11] Ulm Univ, Inst Clin & Expt Trauma Immunol, Ulm, Germany

[12] Ulm Univ, Inst Neurobiochem, Ulm, Germany

[13] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia

来源：

NATURE COMMUNICATIONS | 2023年 / 14卷 / 01期

关键词：

TRANSGENIC MICE; CELL-DEATH; IL-13; NMDA; PHOSPHORYLATION; EXPRESSION; PATHWAYS; CYTOKINE; PLATFORM; INJURY;

D O I：

10.1038/s41467-023-35806-8

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Il-13 is expressed in neurons and IL-13 ko causes memory impairment. Here, authors show that IL-13 and its receptor IL-13Ra1 are pre- and post-synaptic proteins, respectively, involved in synaptic signaling, plasticity and neuroprotection. 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.

引用

页数：21

共 74 条

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