NDLI: Disturbance of neuron–microglia crosstalk mediated by GRP78 in Neuropsychiatric systemic lupus erythematosus mice

Content Provider	Springer Nature : BioMed Central
Author	Xu, Jingyi Yang, Chunshu Zeng, Siyuan Wang, Xuejiao Yang, Pingting Qin, Ling
Abstract	Objectives Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious phenotype of systemic lupus erythematosus (SLE). The disturbance of neuron–microglia crosstalk is recently revealed in many neuropsychiatric diseases but was not well studied in NPSLE. We found glucose regulatory protein 78 (GRP78), a marker of endoplasmic reticulum stress, was significantly increased in the cerebrospinal fluid (CSF) of our NPSLE cohort. We, therefore, investigated whether GRP78 can act as a mediator between the neuron–microglia crosstalk and is involved in the pathogenic process of NPSLE. Methods Serum and CSF parameters were analyzed in 22 NPSLE patients and controls. Anti-DWEYS IgG was injected intravenously into mice to establish a model of NPSLE. Behavioral assessment, histopathological staining, RNA-seq analyses, and biochemical assays were performed to examine the neuro-immunological alterations in the mice. Rapamycin was intraperitoneally administered to define the therapeutic effect. Results The level of GRP78 was elevated significantly in the CSF of the patients with NPSLE. An increase in GRP78 expression, accompanied by neuroinflammation and cognitive impairment, was also found in the brain tissues of the NPSLE model mice induced by anti-DWEYS IgG deposition on hippocampal neurons. In vitro experiments demonstrated that anti-DWEYS IgG could stimulate neurons to release GRP78, which activated microglia via TLR4/MyD88/NFκB pathway to produce more pro-inflammatory cytokines and promote migration and phagocytosis. Rapamycin ameliorated GRP78-inducing neuroinflammation and cognitive impairment in anti-DWEYS IgG-transferred mice. Conclusion GRP78 acts as a pathogenic factor in neuropsychiatric disorders via interfering neuron–microglia crosstalk. Rapamycin may be a promising therapeutic candidate for NPSLE.
Related Links	https://jneuroinflammation.biomedcentral.com/counter/pdf/10.1186/s12974-023-02832-8.pdf
Ending Page	15
Page Count	15
Starting Page	1
File Format	HTM / HTML
ISSN	17422094
DOI	10.1186/s12974-023-02832-8
Journal	Journal of Neuroinflammation
Issue Number	1
Volume Number	20
Language	English
Publisher	BioMed Central
Publisher Date	2023-06-26
Access Restriction	Open
Subject Keyword	Neurosciences Neurology Neurobiology Immunology Neuropsychiatric systemic lupus erythematosus Glucose regulatory protein 78 Microglia Spatial memory Rapamycin
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology Cellular and Molecular Neuroscience Neurology
Journal Impact Factor	9.3/2023
5-Year Journal Impact Factor	9.8/2023

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