The research focus of the Laboratory of Immunology is the control of adaptive immunity, as embodied in the group of leukocytes collectively known as dendritic cells (DC).
Overall, our aspiration is to understand how DC control, induce and modulate the response of the adaptive immune system to challenge, and to use this knowledge to develop new therapeutic and prophylactic modalities towards cancer, infection, allergy and autoimmune disease.
The laboratory is engaged in studies from the basic immunobiology of DC, over the elucidation of the function (or malfunctioning) of DC in various disease processes, to the development of new forms of immunotherapy that exploit the potent capabilities of these cells.
Main areas of research
Presently, the main research programme of the laboratory is directed towards the development of DC-targeted vaccines. These vaccines are specifically constructed to focus antigens on DCs in situ and to promote uptake of the antigen into these cells by intracellular routes that favour subsequent presentation of processed antigen to specific T cells. Furthermore, the vaccine constructs are endowed with properties that should make it possible to functionally modulate the DCs, and thereby predetermine the strength and type of the immune response that is induced by the vaccine. Pilot experiments have shown that targeting antigen to DCs strongly increase the effficacy of vaccination. These multi-functional DC-targeting vaccine constructs represent a completely new generation of vaccines. We, and other researchers working in this area, hope that vaccines of this type could prove efficient not only against infectious diseases like AIDS and malaria but perhaps even constitute new effective weapons in the fight against allergy, autoimmune diseases and cancer.
The vaccine program is carried out in cooperation with professor Svend Birkelund, MD, DMSc, The Laboratory of Medical Mass Spectrometry, Aalborg University, and with senior scientist Lotte Hatting Pugholm, MSc, PhD and Head of Department Kim Varming, MD, PhD both from the Dept. of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark.
DC function in Crohn's disease and modulation by vitamin D
In these studies the function of DCs from normal human subjects, from patients with Crohn’s disease and from patients suffering from severe vitamin D deficiency has been studied, and it has been analysed how the function of these cells may be modulated by vitamin D. The studies have comprise both analyses of the effect of vitamin D on DCs in cultures, as well as studies of DCs obtained from patients before and after oral vitamin D therapy.
This project has been carried out primarily by Lars Erik Bartels, MD as part of the studies for the PhD degree in close collaboration primarily with Head of Department Jens Frederik Dahlerup, DMSc and Head Medical Officer, Associate Professor Jørgen Agnholt, MD, PhD, both from the Gastro-Immuno Research Laboratory (GIRL), Department of medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, Aarhus, Denmark.
The role of DCs in psoriasis
While the aetiology of psoriasis remains elusive, a large body of evidence has implicated DCs as significant in the ongoing inflammatory processes that take place in psoriatic skin.
As part of a PhD project, Rikke Bech, MD has been studying the interplay between DCs and the cytokine milieu in the development and propagation of psoriatic lesions, focusing on another putative key factor, the interleukin-20 (IL-20). In a series of experiments, Rikke has tried to delineate how possible functional abnormalities in DC may affect the disease process.
The experiments has been carried out in collaboration primarily with Head of Department, Professor Knud Kragballe, and Associate Professor, Consultant Lars Iversen, DMSc both at the Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark and John Rømer, Department of Histology, Novo Nordisk, Måløv, Copenhagen, Denmark and with Associate Professor Thomas Vorup-Jensen, PhD at the University of Aarhus.
CEBRA: Development of targeted therapy against glioblastoma multiforme
With Torben Moos, head of the Laboratory of Neurobiology and Vladimir Zachar, head of the Laboratory for Stem Cells Research, Ralf Agger formed the cooperative research center CEBRA (Center for Biomedical Research, Aalborg). In close collaboration with Meg Duroux, head of the Laboratory of Cancer Biology and the Department of Neurosurgery and the Institute of Pathology, both at Aalborg University Hospital, research within this group has sought to define markers on cancer stem cells in patients with glioblastoma multiforme with the ultimate goal of developing a targeted therapy aimed at these cells.