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 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.
Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA; Center for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio, USA.
Mehmet E
ME
Yalvac
Department of Physical Medicine and Rehabilitation, The Ohio State University, Columbus, Ohio, USA; Department of Neurology, The Ohio State University, Columbus, Ohio, USA.
William David
WD
Arnold
Center for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio, USA.
Syed-Rehan A
SA
Hussain
Center for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio, USA.
Cilwyn
C
Braganza
Center for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio, USA.
Kimberly M
KM
Shontz
Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA; Center for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio, USA.
Kelly Reed
KR
Clark
Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA; Center for Vaccines and Immunity, Nationwide Children's Hospital, Columbus, Ohio, USA.
Christopher M
CM
Walker
Department of Neurology, University of Alabama, Birmingham, Alabama, USA.
Eroboghene E
EE
Ubogu
Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA; Center for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio, USA; Department of Neurology, The Ohio State University, Columbus, Ohio, USA. Electronic address: Jerry.Mendell@nationwidechildrens.org.
Jerry R
JR
Mendell
Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA; Center for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio, USA; Department of Neurology, The Ohio State University, Columbus, Ohio, USA. Electronic address: Zarife.Sahenk@nationwidechildrens.org.
Zarife
Z
Sahenk
D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology*; D008297:Male; D051379:Mice; D010523:Peripheral Nervous System Diseases / Q000628:therapy*; D011115:Polyneuropathies / Q000628:therapy*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D014660:Vasoactive Intestinal Peptide