Gene expression analysis of dendritic cells that prevent diabetes in NOD mice: analysis of chemokines and costimulatory molecules

• Published in: Journal of leukocyte biology Vol. 90; no. 3; pp. 539 - 550
• Main Authors: Morel, Penelope A., Srinivas, Mangala, Turner, Michael S., Fuschiotti, Patrizia, Munshi, Rajan, Bahar, Ivet, Feili‐Hariri, Maryam, Ahrens, Eric T.
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.09.2011
• Subjects: Animals; Biomarkers - metabolism; Blotting, Western; Cell Development, Differentiation, and Trafficking; Cell Differentiation; Cell Movement; Cell Proliferation; Cells, Cultured; Chemokines - metabolism; chemotaxis; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - metabolism; diabetes; Diabetes Mellitus - genetics; Diabetes Mellitus - immunology; Diabetes Mellitus - prevention & control; Female; Gene Expression Profiling; Mice; Mice, Inbred NOD; Mice, SCID; Mice, Transgenic; microarray analysis; Oligonucleotide Array Sequence Analysis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; T cells; T-Lymphocytes - immunology; Th1 Cells - immunology; Th2 Cells - immunology
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.0311126

Unique gene expression pattern by dendritic cells that prevents diabetes in NOD mice and induces Th2 and Treg differentiation. 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 19F 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.