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Dendritic cells transduced with lentiviral vectors expressing vasoactive intestinal peptide (VIP) differentiate into tolerogenic‐like DC
Author(s) -
Toscano Miguel Garcia,
Ganea Doina
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1074.33
Subject(s) - vasoactive intestinal peptide , viral vector , immunology , immune system , bone marrow , biology , medicine , receptor , neuropeptide , recombinant dna , biochemistry , gene
It is of increased interest to generate DC with efficient and stable genetic modifications, i.e. expressing a protein with therapeutic effects, to be used as therapeutic tools. Previous results from our laboratory indicated that the neuropeptide VIP has both preventive and therapeutic effects in models of autoimmune diseases such as rheumatoid arthritis and experimental autoimmune encephalomyelitis. We had previously shown that the therapeutic effects of VIP are mediated largely through effects on DC, specifically on the generation of tolerogenic DC. However, direct treatment of human subjects with VIP could lead to significant side effects due to its action on both the cardiovascular system and gastrointestinal tract. Therefore, we used lentiviral vectors carrying the cDNA of human VIP for the transduction of DC during their differentiation from bone marrow cells. Mouse bone marrow DC were efficiently transduced by lentiviral vectors carrying eGFP (up to 60% of cells with an MOI of 10). Use of the same vectors carrying h‐VIP led to a DC population expressing close to 350 pg/ml of VIP. The VIP expressed by transduced DC acted in an autocrine manner; leading to the differentiation of tolerogenic‐like DC, characterized by a reduction in the costimulatory molecules CD40 and CD86 following LPS stimulation. In addition, we observed a downregulation in the production in the pro‐inflammatory cytokines IL‐6 and TNF‐a and an increase in IL‐10 (anti‐inflammatory cytokine). This work was supported by NIH/NIAID R01AI052306