MHC class II-associated invariant chain (Ii) modulates dendritic cells-derived microvesicles (DCMV)-mediated activation of microglia

Abstract

Dendritic cells (DC) - the sentinels of the immune system - play an important role in the maintenance of tolerance and induction of immunity. However, in autoimmune diseases, DC initiate the diseases by presenting self antigens to autoreactive T cells, causing the immune system to mount a response against the body. An example is multiple sclerosis (MS) and its corresponding animal model, experimental autoimmune encephalomyelitis (EAE). During inflammation of the central nervous system (CNS), DC are recruited to activate autoreactive T cells. Microglia - resident mononuclear phagocytes of the brain - also play a role in the pathogenesis of the disease. In this study, we demonstrated that microvesicles derived from DC (DCMV) induced the activation of NF-κB in microglia. Furthermore, MHC class II-associated invariant chain (Ii), also known as CD74, was specifically recruited to DCMV and interestingly, was able to enhance the DCMV-mediated activation of NF-κB in microglia. Thus, this study emphasizes the role of microvesicles and Ii in the communication between DC and microglia. © 2010 Elsevier Inc.