Dataset Information

Transfer of patient's peripheral blood mononuclear cells (PBMCs) disrupts blood-brain barrier and induces anti-NMDAR encephalitis: a study of novel humanized PBMC mouse model.

ABSTRACT:

Background

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune neuropsychiatric disease. Brain access of anti-NMDAR autoantibody through the blood-brain barrier (BBB) is essential for pathogenesis. Most previous animal models limit the investigation of etiologies of BBB damage in patients.

Methods

In this study, we established a novel humanized mouse model of anti-NMDAR encephalitis by intraperitoneal injection of patients' peripheral blood mononuclear cells (PBMCs) into BALB/c Rag2^-/-Il2rg^-/-Sirpα^NODFlk2^-/- mice.

Results

We found that engraftment of patients' PBMCs not only produced potent anti-GluN1 autoantibodies, but also disrupted BBB integrity to allow brain access of autoantibodies, resulting in a hyperactive locomotor phenotype, anxiety- and depressive-like behaviors, cognitive deficits, as well as functional changes in corresponding brain regions. Transcriptome analysis suggested an exaggerated immune response and impaired neurotransmission in the mouse model and highlighted Il-1β as a hub gene implicated in pathological changes. We further demonstrated that Il-1β was produced by endothelial cells and disrupted BBB by repressing tight junction proteins. Treatment with Anakinra, an Il-1 receptor antagonist, ameliorated BBB damage and neuropsychiatric behaviors.

Conclusions

Our study provided a novel and clinically more relevant humanized mouse model of anti-NMDAR encephalitis and revealed an intrinsic pathogenic property of the patient's lymphocytes.

SUBMITTER: Shu Y

PROVIDER: S-EPMC10339507 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

Transfer of patient's peripheral blood mononuclear cells (PBMCs) disrupts blood-brain barrier and induces anti-NMDAR encephalitis: a study of novel humanized PBMC mouse model.

Shu Yaqing Y Peng Fuhua F Zhao Bingchu B Liu Chunxin C Li Qihui Q Li Huilu H Wang Yuge Y Jiang Yanjun Y Lu Tingting T Wang Qin Q Sun Jian J Feng Huiyu H Lu Zhengqi Z Liu Xiaodong X Wang Jie J Qiu Wei W

Journal of neuroinflammation 20230713 1

<h4>Background</h4>Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune neuropsychiatric disease. Brain access of anti-NMDAR autoantibody through the blood-brain barrier (BBB) is essential for pathogenesis. Most previous animal models limit the investigation of etiologies of BBB damage in patients.<h4>Methods</h4>In this study, we established a novel humanized mouse model of anti-NMDAR encephalitis by intraperitoneal injection of patients' peripheral blood mononuclear c ...[more]

PMID: 37443034

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Dataset Information

Transfer of patient's peripheral blood mononuclear cells (PBMCs) disrupts blood-brain barrier and induces anti-NMDAR encephalitis: a study of novel humanized PBMC mouse model.

Background

Methods

Results

Conclusions

Publications

Transfer of patient's peripheral blood mononuclear cells (PBMCs) disrupts blood-brain barrier and induces anti-NMDAR encephalitis: a study of novel humanized PBMC mouse model.

Similar Datasets

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