Ca2+signaling in the regulation of dendritic cell functions

Abstract

Dendritic cells (DCs) are highly versatile antigen-presenting cells critically involved in both innate and adaptive immunity as well as maintenance of self-tolerance. DC function is governed by Ca2+signaling, which directs the DC responses to diverse antigens, including Toll-like receptor ligands, intact bacteria, and microbial toxins. Ca2+-sensitive DC functions include DC activation, maturation, migration, and formation of immunological synapses with T cells. Moreover, alterations of cytosolic Ca2+trigger immune suppression or switch off DC activity. Ca2+signals are generated by the orchestration of Ca2+transport processes across plasma, endoplasmic reticulum, and inner mitochondrial membrane. These processes include active pumping of Ca2+, Ca2+/Na+antiport, and electrodiffusion through Ca2+-permeable channels or uniporters. Ca2+channels in the plasma membrane such as Ca2+release-activated Ca2+or L-type Ca2+channels are tightly regulated by the membrane potential which in turn depends on the activity of voltage-gated K+or Ca2+-activated nonselective cation channels. The rapidly growing knowledge on the function and regulation of these membrane transport proteins provides novel insight into pathophysiological mechanisms underlying dysfunction of the immune system and opens novel therapeutic opportunity to favorably influence the function of the immune system.