Figure 4 Role of chemokines in dendritic cell migration

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Figure 4 Role of chemokines in dendritic cell migration Figure 4 | Role of chemokines in dendritic cell migration. a | Chemotaxis of immature dendritic cells (DCs) is mediated by inflammatory chemokine receptors such as CC-chemokine receptor 6 (CCR6), which guide these DCs to stressed tissues through interaction with CC-chemokine ligand 20 (CCL20). At the inflamed site, sensing of damage-associated molecular patterns (DAMPs) triggers the upregulation of CCR7 at the surface of DCs. Activated DCs home to lymph nodes through afferent lymphatics and their migration is guided by CCL19 and CCL21 (two ligands of CCR7), which are expressed by stromal cells in the T-cell area of secondary lymphoid organs. b | In rheumatoid arthritis (RA), immature DCs and monocytes are attracted to the inflamed joint by synoviocytes that express CCL20 and CXC-chemokine ligand 10 (CXCL10) under the stimulation of TNF, IL-1β and IL-17. This process leads to an accumulation of immature DCs, which contributes to osteoclastogenesis through the RANK–RANKL pathway. Upon exposure to DAMPs, DCs mature and, in some conditions, accumulate in ectopic lymphoid structures (ELS), the formation of which is dependent on lymphotoxins, CCL21, CXCL13 and IL-17. Infiltrating monocytes differentiate into inflammatory DCs in the presence of DAMPs and granulocyte-macrophage colony-stimulating factor (GM-CSF). Inflammatory DCs (infDCs) secrete high levels of IL-23, IL-6, TGFβ and IL-1β, which induce the differentiation of T helper type 17 (TH17) cells. TH17 cells promote in turn the formation of ELS through the secretion of IL-17. In ELS, the differentiation of B cells into high-affinity autoreactive plasma cells leads to the release of disease-specific autoantibodies such as anti-citrullinated protein antibodies (ACPAs). Coutant, F. & Miossec, P. (2016) Altered dendritic cell functions in autoimmune diseases: distinct and overlapping profiles Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2016.147