Regulation of the tolerogenic function of steady-state DCs

Dendritic cells (DCs) are master regulators of T-cell responses. After sensing pathogen-derived molecular patterns (PAMPs), or signals of inflammation and cellular stress, DCs differentiate into potent activators of naïve CD4(+) and CD8(+) T cells through a process that is termed DC maturation. By contrast, DCs induce and maintain peripheral T-cell tolerance in the steady state, that is in the absence of overt infection or inflammation. However, the immunological steady state is not devoid of DC-activating stimuli, such as commensal microorganisms, subclinical infections, or basal levels of proinflammatory mediators. In the presence of these activating stimuli, DC maturation must be calibrated to ensure self-tolerance yet allow for adequate T-cell responses to infections. Here, we review the factors that are known to control DC maturation in the steady state and discuss their effect on the tolerogenic function of steady-state DCs.