IL-26 Is Overexpressed in Rheumatoid Arthritis and Induces Proinflammatory Cytokine Production and Th17 Cell Generation

Interleukin-26 (il-26),a member of the il-10 cytokine family,induces the production of proinflammatory cytokines by epithelial cells. il-26 has been also reported overexpressed in crohn's disease,suggesting that it may be involved in the physiopathology of chronic inflammatory disorders. here,we have analyzed the expression and role of il-26 in rheumatoid arthritis (ra),a chronic inflammatory disorder characterized by joint synovial inflammation. we report that the concentrations of il-26 are higher in the serums of ra patients than of healthy subjects and dramatically elevated in ra synovial fluids compared to ra serums. immunohistochemistry reveals that synoviolin+ fibroblast-like synoviocytes and cd68+ macrophage-like synoviocytes are the main il-26-producing cells in ra joints. fibroblast-like synoviocytes from ra patients constitutively produce il-26 and this production is upregulated by il-1-beta and il-17a. we have therefore investigated the role of il-26 in the inflammatory process. results show that il-26 induces the production of the proinflammatory cytokines il-1-beta,il-6,and tumor necrosis factor (tnf)-alpha by human monocytes and also upregulates the expression of numerous chemokines (mainly ccl20). interestingly,il-26-stimulated monocytes selectively promote the generation of rorgamma t+ th17 cells,through il-1-beta secretion by monocytes. more precisely,il-26-stimulated monocytes switch non-th17 committed (il-23r- or ccr6- cd161-) cd4+ memory t cells into th17 cells. finally,synovial fluids from ra patients also induce th17 cell generation and this effect is reduced after il-26 depletion. these findings show that il-26 is constitutively produced by ra synoviocytes,induces proinflammatory cytokine secretion by myeloid cells,and favors th17 cell generation. il-26 thereby appears as a novel proinflammatory cytokine,located upstream of the proinflammatory cascade,that may constitute a promising target to treat ra and chronic inflammatory disorders. © 2012 corvaisier et al.