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

Journal of Leukocyte Biology

Rajan Munshi²  Mangala Srinivas¹  Patrizia Fuschiotti³  Eric T. Ahrens¹  Ivet Bahar²  Maryam Feili-Hariri–,3 and³  Michael S. Turner³  Penelope A. Morel ⁴ 

[1] Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA –Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA;Computational and Systems Biology, and –Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA;Departments of Immunology, –Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA;Departments of Immunology,  Medicine, –Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA;

关键词: diabetes;    T cells;    chemotaxis;    microarray analysis;   

DOI  :  10.1189/jlb.0311126

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown