Effects of pro-inflammatory cytokines and cell interactions on cell area and cytoskeleton of rheumatoid arthritis synoviocytes and immune cells

Rheumatoid synovitis is infiltrated by immune cells that interact with synoviocytes, leading to the pannus for-mation. Inflammation or cell interaction effects are mainly evaluated with cytokine production, cell proliferation or migration. Few studies interest on cell morphology. Here, the purpose was to deepen some morphological changes of synoviocytes or immune cells under inflammatory conditions. Inflammatory cytokines, IL-17 and TNF that are largely involved in RA pathogenesis, induced a change in synoviocyte morphology, inducing a retracted cell with higher number of pseudopodia. Several morphological parameters decreased in inflammatory condi-tions: cell confluence, area and motility speed. The same impact on cell morphology was observed in co-culture of synoviocytes and immune cells in inflammatory/non-inflammatory conditions or with cell activation (miming the in vivo situation), affecting both cell types: synoviocytes were retracted and inversely immune cells prolif-erated, indicating that cell activation induced a morphological change of cells. In contrast, with RA but not control synoviocytes, cell interactions were not sufficient to affect PBMC and synoviocyte morphology. The morphological effect came only from the inflammatory environment. These findings reveal that the inflammatory environment or cell interactions induced massive changes in control synoviocytes, with cell retraction and in-crease of pseudopodia number, leading to better interactions with other cells. Except in the case of RA, the inflammatory environment was absolutely required for such changes.