期刊
JOURNAL OF AUTOIMMUNITY
卷 91, 期 -, 页码 34-44出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jaut.2018.03.001
关键词
Lupus; Neuropsychiatric-lupus (NPSLE); Blood-brain barrier (BBB); Blood-CSF barrier (BCSFB); Autoantibodies; Choroid plexus (CP)
类别
资金
- Abisch-Frenkel Foundation [15/H1]
- Leona M. and Harry B. Helmsley Charitable Trust [2015PG-ISL007]
- National Institute of Arthritis and Musculoskeletal Diseases [AR065594]
- NIH [T32-GM007288]
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR065594] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM007288] Funding Source: NIH RePORTER
The pathogenesis of neuropsychiatric lupus (NPSLE) is believed to include the entry of circulating neuropathic antibodies to,the brain via a pathologically permeable blood-brain barrier (BBB). Nevertheless, direct evidence of BBB pathology or mechanisms underlying BBB dysfunction is missing. Here, we examined BBB integrity in an established NPSLE mouse model (MRL/fas(1Pr)/(lP1)). Surprisingly, challenging the barrier with various exogenous tracers demonstrated insignificant changes in BBB permeability. Furthermore, electron microscopy showed no ultrastructure changes supporting hyper permeability. However, we found that abnormal function of the blood-cerebrospinal fluid barrier (BCSFB) in the choroid plexus underlies brain exposure to neuropathic antibodies. Considerable intrathecal lymphocyte infiltration likely occurs through the BCSFB, accompanied by epithelial hyper permeability to antibodies. Our results challenge the commonly held view of BBB disruption in NPSLE, supporting a shift in focus to BCSFB dysfunction as a causative factor in the disease. (C) 2018 Elsevier Ltd. All rights reserved.
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