Dendritic cells in systemic lupus erythematosus: From pathogenesis to therapeutic applications.

ABSTRACT

Systemic lupus erythematosus (SLE) is a severe chronic systemic autoimmune disease caused by complicated interactions among genetic, epigenetic, and immunological factors. Dendritic cells (DCs), as the most important antigen-presenting cells, play pivotal roles in both triggering pathogenic autoimmune responses, and also maintaining immune tolerance. Distinct DC subsets are endowed with diversified phenotypic and functional characteristics, and play variable roles in shaping immunity and tolerance during the development of SLE. Abnormal activation or disabled tolerance of DCs not only triggers aberrant production of inflammatory mediators and type I interferons leading to pathogenic innate immunity and autoinflammation, but also causes an imbalance of effector versus regulatory T cell responses and sustained production of auto-antibodies from B cells, leading to continuously amplified autoimmune pathogenesis in SLE. Over the past decade, significant progress has been made in revealing the changes of DC accumulation or function in SLE, and how the functional dysregulations of DCs contribute to the pathological inflammation of SLE, leading to breakthroughs in DC-based therapeutics in the treatment of SLE. In this review, we review the recent advances in the activation and function of the major DC subsets in the pathogenesis of SLE as well as the therapeutic potential of targeting DC subset or status against SLE.