The potential use of dendritic cells in mouse models of atherosclerosis

Atherosclerosis is a chronic inflammatory disease of the vasculature in which both a disturbed lipid metabolism and inflammatory immune responses against several self-antigens are involved. In this thesis we have explored the effectiveness of DC-immunotherapy in atherosclerosis. We have used different strategies to target the immune component in different stages of atherosclerosis. First we used DCs as a vaccination strategy to induce a protective antibody response trough the injection of oxLDL-pulsed DCs or to target NKT cells by the injection of OCH-pulsed DCs. Next we assessed the potential of DC-immunotherapy in a model of established atherosclerosis. We also evaluated the effects of a disturbed TGF-_ signaling in DCs and the subsequent effects on atherosclerosis by using ApoE-/- which have a dysfunctional TGF-__ Receptor II under the CD11c promoter. Next, we were interested in the effect of foam-cell formation on the antigen-presenting capacity of DCs and macrophages. Therefore we studied the effect of oxLDL-loading on antigen uptake and antigen presentation by DCs and macrophages. Finally, by depleting or inducing Tregs we investigated the potential role of regulatory T cells in a mouse model for aneurysm formation

The potential use of dendritic cells in mouse models of atherosclerosis

Atherosclerosis is a chronic inflammatory disease of the vasculature in which both a disturbed lipid metabolism and inflammatory immune responses against several self-antigens are involved. In this thesis we have explored the effectiveness of DC-immunotherapy in atherosclerosis. We have used different strategies to target the immune component in different stages of atherosclerosis. First we used DCs as a vaccination strategy to induce a protective antibody response trough the injection of oxLDL-pulsed DCs or to target NKT cells by the injection of OCH-pulsed DCs. Next we assessed the potential of DC-immunotherapy in a model of established atherosclerosis. We also evaluated the effects of a disturbed TGF-_ signaling in DCs and the subsequent effects on atherosclerosis by using ApoE-/- which have a dysfunctional TGF-__ Receptor II under the CD11c promoter. Next, we were interested in the effect of foam-cell formation on the antigen-presenting capacity of DCs and macrophages. Therefore we studied the effect of oxLDL-loading on antigen uptake and antigen presentation by DCs and macrophages. Finally, by depleting or inducing Tregs we investigated the potential role of regulatory T cells in a mouse model for aneurysm formation.Leiden University LACDR Hartstichting Genzyme Beckman Coulter Special Diet Services (Tecnilab-BMI)UBL - phd migration 201

Platelets and autoimmunity

Pathophysiology and treatment of rheumatic disease

Expansion of Th17 Cells by Human Mast Cells Is Driven by Inflammasome-Independent IL-1 beta

Pathophysiology and treatment of rheumatic disease

Anti-citrullinated protein antibodies contribute to platelet activation in rheumatoid arthritis

Pathophysiology and treatment of rheumatic disease

Foam cell formation affects MHCI processing and presentation in vitro while hypercholesteremia induces a DC-like phenotype in macrophages in vivo

Pathophysiology and treatment of rheumatic disease

Abatacept decreases disease activity in a absence of CD4(+) T cells in a collagen-induced arthritis model

Pathophysiology and treatment of rheumatic disease

Vaccination against Foxp3+ regulatory T cells aggravates atherosclerosis

Regulatory T cells are crucial for immune homeostasis and an impaired regulatory T cell function results in many pathological conditions. Regulatory T cells have already been described to be protective in atherosclerosis. However the exact contribution of Foxp3-expressing natural regulatory T cells in atherosclerosis has not been elucidated yet. In this study we vaccinated LDL receptor deficient mice with dendritic cells which are transfected with Foxp3 encoding mRNA and studied the effect on initial atherosclerosis. Vaccination against Foxp3 resulted in a reduction of Foxp3+ regulatory T cells in several organs and in an increase in initial atherosclerotic lesion formation. Furthermore we observed an increase in plaque cellularity and increased T cell proliferation in the Foxp3 vaccinated mice. We further establish the protective role of Tregs in atherosclerosis. The results illustrate the important role for Foxp3-expressing regulatory T cells in atherosclerosis, thereby providing a potential opportunity for therapeutic intervention against this disease

Repeated Fc epsilon RI triggering reveals modified mast cell function related to chronic allergic responses in tissue

Molecular Technology and Informatics for Personalised Medicine and Healt