1. Figure 2 Involvement of plasmacytoid dendritic cells
in the induction and amplification of autoimmunity in systemic lupus erythematosus
Figure 2 | Involvement of plasmacytoid dendritic cells in the induction and amplification of autoimmunity in systemic lupus erythematosus. Nuclear autoantigens (such as histones, ribonucleoproteins, Ro/SSA and La/SSB) complexed with autoantibodies are internalized via low-affinity immunoglobulin gamma Fc region receptor IIa (FcγRIIa) and induce type I interferon (IFN) production by plasmacytoid dendritic cells (pDCs) through engagement of endosomal Toll-like receptors. IFNs, in synergy with self DNA and self RNA complexes released by dying cells, induce the maturation of conventional dendritic cells (DCs). Activation of DCs induced by IFNs promotes the differentiation of CD8+ T lymphocytes into cytotoxic T lymphocytes (CTLs) and the polarization of CD4+ T cells into T helper type 1 (TH1) cells and TH17 cells. Cell lysis induced by CTLs generates nucleosomes and other autoantigens, whereas IL-17 fuels tissue damage by recruiting inflammatory cells. IFN-induced DC maturation also promotes the secretion of B cell activating factor (BAFF, also known as TNF ligand superfamily member 13B) and a proliferation-inducing ligand (APRIL, also known as TNF ligand superfamily member 13), which are involved in the survival of autoreactive plasma cells and the generation of autoantibodies. In the spleen, marginal zone B cells (MZ B cells) are essential for the maintenance of marginal zone macrophages (MZMs) that surround the splenic follicles. MZMs act as a follicular exclusion barrier against antigens derived from apoptotic cells, which is crucial in the induction and maintenance of tolerance. In SLE, pDCs accumulate in the marginal zone and their secretion of IFNs interferes with the crosstalk between MZ B cells and MZMs. This process leads to the follicular translocation of MZ B cells, the inability of MZMs to clear apoptotic cells and loss of tolerance to autoantigens. In the follicle, MZ B cells stimulate germinal centre (GC) reactions that result in autoantibody production. icDC, immature conventional dendritic cell; mcDC, mature conventional dendritic cell.
Coutant, F. & Miossec, P. (2016) Altered dendritic cell functions in autoimmune diseases: distinct and overlapping profiles
Nat. Rev. Rheumatol. doi: /nrrheum