Figure 3.

Synovial CD1c⁺ dendritic cell (DC)‐mediated chemoattraction, T cell activation and polarization. Intra‐articular DCs secrete multiple chemokines, including chemokine (C‐C motif) ligand 3 (CCL3), CCL17, C‐X‐C motif chemokine ligand19 (CXCL19) and CXCL10, to induce T cell migration to the rheumatoid arthritis (RA) synovium. RA synovial CD1c⁺ DCs also secrete chemokines (including CCL3 and CXCL8) that attract proinflammatory immune cells, including macrophages, neutrophils and monocytes. RA synovial CD1c⁺ DCs have enhanced expression of human leucocyte antigen D‐related (HLA‐DR) and co‐stimulatory molecules CD40, CD80 and CD86 required for T cell activation. Synovial CD1c⁺ DCs from RA patients produce cytokines required for T cell polarization towards T helper type 17 (Th17) [interleukin (IL)‐1β, IL‐6, and IL‐23] and Th1 (IL‐12) differentiation. Synovial fluid from seropositive RA patients show high levels of serum soluble (s) programmed cell death 1 (PD‐1), which may interfere with the PD‐1/programmed death ligand 1 (PD‐L1) inhibitory signalling loop. This figure was generated using the Motfolio PPT Drawing Toolkits (www.motfolio.com), and knee image was obtained from https://www.pearsonschoolsandfecolleges.co.uk/FEAndVocational/SportsStudies/ALevel/OCRALevelPE2008/Samples/SamplepagesfromOCRASPEStudentBook/chapter1_sample.pdf, page 7, figure 1.4.