1. Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2016.147
Figure 3 Dendritic cell subsets in the rheumatoid arthritis synovium and inflamed muscle
Figure 3 | Dendritic cell subsets in the rheumatoid arthritis synovium and inflamed muscle. a | In the rheumatoid arthritis (RA) synovium, monocytes exit blood vessels and enter the synovial tissue, where they differentiate into inflammatory DCs (infDCs) in the presence of danger-associated molecular patterns (DAMPs) and of granulocyte-macrophage colony-stimulating factor (GM-CSF) produced by IL-12-stimulated CD4+ T cells. infDCs can in turn contribute to the generation of GM-CSF-producing T cells. After crossing the synovial lining, infDCs activate T helper type 17 (TH17) cells. In response to local inflammation and the chemoattractant CC-chemokine ligand 20 (CCL20), immature conventional DCs (icDCs) and TH17 cells exit blood vessels and infiltrate the synovial tissue. By sensing DAMPs and proinflammatory cytokines, a local maturation process occurs, leading to the formation of fully mature DCs (mDCs), which are trapped within lymphocytic aggregates and promote TH1 responses by the secretion of IL-12. Plasmacytoid DCs (pDCs) also infiltrate the RA synovium and release type I interferons (IFNs). The absence of CC-chemokine receptor 7 (CCR7) expression at the surface of DCs impairs DC-dependent migration, thus leading to DC accumulation in the synovial tissue, which contributes to osteoclastogenesis by the secretion of receptor activator of nuclear factor κB ligand (RANKL). b | In muscle, icDCs are attracted by the local secretion of CCL20 in inflamed tissue and are activated by DAMPs. Secretion of IL-12 and IL-23 by mature DCs supports the accumulation and effector functions of CD8+ T cells, as well as the polarization of CD4+ T cells into TH1 and TH17 cells. In polymyositis (left side), IL-17 acts in synergy with IL-1β and TNF to upregulate the expression of MHC class I molecules at the surface of myocytes, making them targets for cytotoxic T cells. These T cells induce myofibre necrosis by the release of perforin 1 and granzyme B. In dermatomyositis (right side), pDCs are over-represented and might contribute to autoreactive B-cell responses by inducing plasma-cell differentiation through IFN secretion. mDCs stimulate CD4+ TH cells that in turn stimulate B cells and autoantibody production.
Coutant, F. & Miossec, P. (2016) Altered dendritic cell functions in autoimmune diseases: distinct and overlapping profiles
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