Dendritic cells and immuno-modulation in autoimmune arthritis

Abstract

The immune system consists of a broad array of immune cells to protect the body against invasive pathogenic microorganisms. Immune responses should however, be tightly controlled to ensure tolerance to the body’s own cells and proteins in order to limit damage to the host own cells and tissue. Autoimmune diseases can arise when the balance between pathogen-driven immunity (inflammatory immune response) and tolerance (regulatory immune response) to self products is dysregulated. Dendritic cells are immune cells with the ability to direct immune responses towards an inflammatory or regulatory immune reaction. During immune homeostasis, i.e. in the absence of infectious or inflammatory stimulation, dendritic cells reside in state that contributes to immune tolerance. In this condition, dendritic cells are a promising immunotherapeutic target in autoimmune diseases. These tolerance inducing properties can be enhanced and stabilized under laboratory conditions. Stress proteins are imperative for the maintenance of cellular homeostasis and are especially produced after forms of stress like: increased temperature (fever), nutritional deficiency and exposure to toxins, inflammatory mediators and viral infections. Stress proteins are also highly immunogenic and have the potential to induce immuno-regulatory pathways. The research described in this dissertation focuses on the in vitro induction and stabilization of a regulatory phenotype in dendritic cells via administration of stress proteins to dendritic cells, or otherwise via treatment of dendritic cells with a physiological stress to ensure production of stress proteins by dendritic cells. Their potential regulatory role was studied in an experimental mouse model of rheumatoid arthritis. In addition, the immune-regulatory role of dendritic cells during immune homeostasis was studied in more detail