Immunomodulation of autoimmune diabetes by dendritic cells

Abstract

The biology and properties of dendritic cells (DCs) have been intensely studied in the research areas of infectious diseases, tumor immunology, and vaccine development. This unique subset of immune cells has recently also moved to the center of interest for basic and clinical research in autoimmunity, owing not only to the extraordinary importance of DCs in the initiation and sustenance of adaptive immune responses, but also to more recent discoveries about their profound ability to control and downregulate ongoing T-cell responses. We review current progress of using DCs in mice for induction and propagation of autoimmune T-cell responses and their therapeutic potential to dampen or even stop beta-cell-specific autoimmunity. Finally, we offer our perspective on how basic research progress in DC technology, mostly from mouse models, may translate into emerging diagnostic and therapeutic applications for human type 1 diabetes.

Immunogenicity of Therapeutic Fusion Proteins: Contributory Factors and Clinical Experience

“…Such iDC express low amounts of CD80/CD86, and thus provide little of the co-stimulation necessary to generate a robust adaptive response [64]. However, maintaining this immature phenotype in vivo can be challenging.…”

Can we prevent immunogenicity of human protein drugs?

“…The primary focus has been on tolerogenic immature dendritic cells (iDCs) that are pulsed with target antigens. Such iDCs express low amounts of CD80/CD86 and thus provide little co-stimulation 26. Maintaining this immature phenotype in vivo is an important caveat.…”

Dendritic cells in tolerance induction for the treatment of autoimmune diseases

“…The importance of DC in maintaining tolerance is clearly demonstrated by the fatal autoimmunity observed in animals with constitutive ablation of DC [2]. Given their dual function, it is not surprising that DC have been shown to exert both pathogenic and protective properties in several autoimmune diseases, including inflammatory bowel and celiac disease [3], rheumatoid arthritis (RA) [4], type 1 diabetes [5], autoimmune pancreatitis [6] and multiple sclerosis [7].…”