PMID- 20068554
OWN - NLM
STAT- MEDLINE
DCOM- 20100730
LR  - 20211020
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 18
IP  - 5
DP  - 2010 May
TI  - Dendritic cells transduced with lentiviral vectors expressing VIP differentiate 
      into VIP-secreting tolerogenic-like DCs.
PG  - 1035-45
LID - 10.1038/mt.2009.293 [doi]
AB  - Dendritic cells (DCs) initiate immune responses as well as tolerance. We showed 
      previously that the neuropeptide vasoactive intestinal peptide (VIP) suppresses 
      innate immune responses, modulates adaptive responses by generating regulatory T 
      cells (Treg) through the induction of tolerogenic DCs (tDCs), and has therapeutic 
      effects in models of autoimmune/inflammatory disorders. Systemic VIP 
      administration is limited by its short biological half-life and by its 
      pleiotropic effects on the cardiovascular system and gastrointestinal tract. 
      Therefore, we used lentiviral vectors to genetically engineer VIP-expressing bone 
      marrow-derived DC (BMDC) and characterized the transduced LentiVIP-DC in terms of 
      phenotype and therapeutic effects in models of experimental autoimmune 
      encephalomyelitis (EAE) and cecal ligation and puncture (CLP) sepsis. 
      LentiVIP-DCs secrete VIP, and resemble tDCs through lack of co-stimulatory 
      molecule upregulation, lack of proinflammatory cytokine secretion, increased 
      interleukin (IL)-10 production, and poor stimulation of allogeneic T cells. A 
      single inoculation of LentiVIP-DC in EAE or CLP mice had therapeutic effects, 
      which correlated with reduced expression of proinflammatory cytokines and 
      increased IL-10 production in spinal cord and peritoneal fluid, respectively. In 
      contrast to systemic VIP administration that requires repeated, high-dose 
      inoculations, local delivery of VIP by LentiVIP-DC may represent a promising 
      therapeutic tool for the treatment of autoimmune diseases and inflammatory 
      disorders.
FAU - Toscano, Miguel G
AU  - Toscano MG
AD  - Department of Microbiology and Immunology, Temple University School of Medicine, 
      Philadelphia, Pennsylvania, USA.
FAU - Delgado, Mario
AU  - Delgado M
FAU - Kong, Weimin
AU  - Kong W
FAU - Martin, Francisco
AU  - Martin F
FAU - Skarica, Mario
AU  - Skarica M
FAU - Ganea, Doina
AU  - Ganea D
LA  - eng
GR  - R01 AI047325/AI/NIAID NIH HHS/United States
GR  - R01 AI052306/AI/NIAID NIH HHS/United States
GR  - R01AI052306/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100112
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 37221-79-7 (Vasoactive Intestinal Peptide)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/cytology
MH  - Cell Differentiation/genetics/*physiology
MH  - Cell Movement/genetics/physiology
MH  - Cells, Cultured
MH  - Dendritic Cells/*cytology/*metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Genetic Vectors
MH  - Lentivirus
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transduction, Genetic/*methods
MH  - Vasoactive Intestinal Peptide/genetics/*metabolism
PMC - PMC2890107
EDAT- 2010/01/14 06:00
MHDA- 2010/07/31 06:00
PMCR- 2011/05/01
CRDT- 2010/01/14 06:00
PHST- 2010/01/14 06:00 [entrez]
PHST- 2010/01/14 06:00 [pubmed]
PHST- 2010/07/31 06:00 [medline]
PHST- 2011/05/01 00:00 [pmc-release]
AID - S1525-0016(16)31036-X [pii]
AID - 10.1038/mt.2009.293 [doi]
PST - ppublish
SO  - Mol Ther. 2010 May;18(5):1035-45. doi: 10.1038/mt.2009.293. Epub 2010 Jan 12.