Altered dendritic cell functions in autoimmune diseases: distinct and overlapping profiles.

ABSTRACT

Dendritic cells (DCs) are central regulators of the balance between immunity and tolerance, and alteration of the specialized DC system is a common feature of both systemic and tissue-specific autoimmune diseases. Increasing evidence indicates that the heterogeneity and the remarkable functional diversity of DC subsets might be differentially affected in autoimmune disorders, which accounts for different pathologies. This Review discusses recent findings that support this concept and provides a new conceptual overview of the altered function and distribution of DCs in autoimmune disorders. The discussion will focus on systemic lupus erythematosus - a prototype of a multi-organ disease - as well as rheumatoid arthritis and idiopathic inflammatory myopathies, pathologies characterized by tissue-specific lesions. Studies on these diseases have revealed common and disease-specific changes in DC distribution and in critical DC functions, such as phagocytosis, cytokine secretion and migration. An improved understanding of the roles of altered DC distribution and/or disturbed key functions in these autoimmune diseases will pave the way for the development of new therapies aiming at reducing immunogenicity and at enhancing the tolerogenic capacity of DCs. Although some tolerogenic DCs have already been introduced in the clinic, the successful translation of other DC-based therapies will require considerable research efforts.