Figure 1

Role of the type I interferon system in the etiopathogenesis of lupus. A viral infection induces IFNα production in plasmacytoid dendritic cells (pDCs) and the release of autoantigens from dying cells. Produced IFNα promotes maturation of monocytes to dendritic cells, activation of T cells and stimulation of B cells, as described in the text. In individuals with a genetic set-up that causes a strong IFNα production and/or a marked IFNα response, tolerance is broken and antibodies against nucleic-acid-containing autoantigens are produced. The autoantibodies, together with the autoantigens, form interferogenic immune complexes (ICs) that act as endogenous inducers of IFNα production in pDCs. In addition, these ICs can directly stimulate the B cells to increased autoantibody production. UV-light induced apoptosis will increase the release of autoantigens, which will result in the formation of more interferogenic ICs. All these events will establish a vicious circle with an ongoing production of IFNα by the pDCs and a continuous exposure of the immune system to IFNα that maintains the autoimmune process. Natural killer (NK) cells promote the IFNα production, and activated monocytes downregulate the NK cells, but the monocyte function seems to be deficient in lupus. Figure modified from [87]. DC, dendritic cell; Mo, monocyte; TCR, T-cell receptor.