12 research outputs found
Aberrant regulation of interleukin-12 receptor beta2 chain on type 1 cytokine-stimulated T lymphocytes in type 1 diabetes
Poor in vitro induction of FOXP3 and ICOS in type 1 cytokine environment activated T-cells from children with type 1 diabetes
Reduced CCR4, interleukin-13 and GATA-3 up-regulation in response to type 2 cytokines of cord blood T lymphocytes in infants at genetic risk of type 1 diabetes
Poor in vitro maturation and pro-inflammatory cytokine response of dendritic cells in children at genetic risk of type 1 diabetes.
Decreased in vitro type 1 immune response against Coxsackie virus B4 in children with type 1 diabetes
Decreased In Vitro Type 1 Immune Response Against Coxsackie Virus B4 in Children With Type 1 Diabetes
A novel pancreatic β-cell targeting bispecific-antibody (BsAb) can prevent the development of Type 1 diabetes in NOD mice
The gene expression profile of CD11c<sup>+</sup>CD8α<sup>-</sup> dendritic cells in the pre-diabetic pancreas of the NOD mouse
Two major dendritic cell (DC) subsets have been described in the pancreas of mice: The CD11c+CD8α- DCs (strong CD4+ T cell proliferation inducers) and the CD8α+CD103+ DCs (T cell apoptosis inducers). Here we analyzed the larger subset of CD11c +CD8-- DCs isolated from the pancreas of pre-diabetic NOD mice for genome-wide gene expression (validated by Q-PCR) to elucidate abnormalities in underlying gene expression networks. CD11c +CD8α- DCs were isolated from 5 week old NOD and control C57BL/6 pancreas. The steady state pancreatic NOD CD11c +CD8α- DCs showed a reduced expression of several gene networks important for the prime functions of these cells, i.e. for cell renewal, immune tolerance induction, migration and for the provision of growth factors including those for beta cell regeneration. A functional in vivo BrdU incorporation test showed the reduced proliferation of steady state pancreatic DC. The reduced expression of tolerance induction genes (CD200R, CCR5 and CD24) was supported on the protein level by flow cytometry. Also previously published functional tests on maturation, immune stimulation and migration confirm the molecular deficits of NOD steady state DC. Despite these deficiencies NOD pancreas CD11c+CD8α- DCs showed a hyperreactivity to LPS, which resulted in an enhanced pro-inflammatory state characterized by a gene profile of an enhanced expression of a number of classical inflammatory cytokines. The enhance