VIP-expressing Dendritic Cells Protect Against Spontaneous Autoimmune Peripheral Polyneuropathy

The spontaneous autoimmune peripheral polyneuropathy (SAPP) model in B7-2 knockout nonobese diabetic mice mimics a progressive and unremitting course of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). In this study, bone marrow–derived dendritic cells (DCs) were transduced to expre...

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Bibliographic Details
Published in:Molecular therapy 2014-07, Vol.22 (7), p.1353-1363
Main Authors: Yalvac, Mehmet E, Arnold, William David, Hussain, Syed-Rehan A, Braganza, Cilwyn, Shontz, Kimberly M, Clark, Kelly Reed, Walker, Christopher M, Ubogu, Eroboghene E, Mendell, Jerry R, Sahenk, Zarife
Format: Article
Language:English
Subjects:
Animals
Antigens
Cells, Cultured
Dendritic cells
Dendritic Cells - cytology
Dendritic Cells - metabolism
Dendritic Cells - physiology
Diabetes
Enzymes
Experiments
Gene therapy
Immunoassay
Male
Mice
Original
Peripheral Nervous System Diseases - therapy
Polyneuropathies - therapy
Polypeptides
Vasoactive Intestinal Peptide - metabolism
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Summary:The spontaneous autoimmune peripheral polyneuropathy (SAPP) model in B7-2 knockout nonobese diabetic mice mimics a progressive and unremitting course of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). In this study, bone marrow–derived dendritic cells (DCs) were transduced to express vasoactive intestinal polypeptide (VIP) using a lentiviral vector (LV-VIP). These transduced DCs (LV-VIP-DCs) were then injected intravenously (i.v.) into 16-week-old (before disease onset) and 21-week-old (after disease onset) SAPP mice in order to prevent or attenuate the disease. Outcome measures included behavioral tests, clinical and histological scoring, electrophysiology, real-time PCR, flow cytometry analyses, and enzyme-linked immunosorbent assay. LV-VIP-DCs were recruited to the inflamed sciatic nerve and reduced the expression of inflammatory cytokines. A single injection of LV-VIP-DC delayed the onset of disease, stabilized, and attenuated clinical signs correlating with ameliorated behavioral functions, reduced nerve demyelination, and improved nerve conduction. This proof-of-principle study is an important step potentially leading to a clinical translational study using DCs expressing VIP in cases of CIDP refractory to standard immunosuppressive therapy.
ISSN:1525-0016
1525-0024
DOI:10.1038/mt.2014.77