title: Gene expression analysis of dendritic cells that prevent diabetes in NOD mice: analysis of chemokines and costimulatory molecules.
abstract: We have demonstrated previously that BM-derived DCs can prevent diabetes development and halt progression of insulitis in NOD mice, the mouse model of type 1 diabetes. The DC population that was most effective in this therapy had a mature phenotype, expressed high levels of costimulatory molecules, and secreted low levels of IL-12p70. The protective DC therapy induced Treg and Th2 cells in vitro and in vivo. Microarray analysis of therapeutic and nontherapeutic DC populations revealed differences in the expression of OX40L, CD200, Ym-1, CCL2, and CCL5, which could play important roles in the observed DC-mediated therapy. The unique pattern of costimulatory molecules and chemokines expressed by the therapeutic DCs was confirmed by flow cytometry and ELISA. Using a novel cell-labeling and (19)F NMR, we observed that the chemokines secreted by the therapeutic DCs altered the migration of diabetogenic Th1 cells in vivo and attracted Th2 cells. These results suggest that the therapeutic function of DCs is mediated by a combination of costimulatory and chemokine properties that results in the attraction of diabetogenic Th1 and the induction of Th2 and/or Treg differentiation.
authors.affiliation: Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA. morel@pitt.edu
authors.forename: Penelope A
authors.initials: PA
authors.lastname: Morel
authors.forename: Mangala
authors.initials: M
authors.lastname: Srinivas
authors.forename: Michael S
authors.initials: MS
authors.lastname: Turner
authors.forename: Patrizia
authors.initials: P
authors.lastname: Fuschiotti
authors.forename: Rajan
authors.initials: R
authors.lastname: Munshi
authors.forename: Ivet
authors.initials: I
authors.lastname: Bahar
authors.forename: Maryam
authors.initials: M
authors.lastname: Feili-Hariri
authors.forename: Eric T
authors.initials: ET
authors.lastname: Ahrens
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D003920:Diabetes Mellitus / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D005260:Female; D020869:Gene Expression Profiling; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D015415:Biomarkers; D018925:Chemokines; D012333:RNA, Messenger