Structural cell heterogeneity underlies the differential contribution of IL-17A, IL-17F and IL-23 to joint versus skin chronic inflammation.

The current therapeutic strategy used in immune-mediated inflammatory diseases (IMIDs) primarily targets immune cells or associated-pathways. However, recent evidence suggests that the microenvironment modulates immune cell development and responses. During inflammation, structural cells acquire a pathogenetic phenotype and the interactions with immune cells are often greatly modified. Understanding the importance of these tissue-specific interactions may allow to explain why some biologics are effective in some IMIDs but not in others. The differential effects of interleukin (IL)-17 A, IL-17F and IL-23 in joint versus skin inflammation depends on structural cell heterogeneity. In addition, the sometimes opposite effects of immune/structural cell interactions on the production of these cytokines illustrate the importance of these cells in chronic inflammation, using the examples of rheumatoid arthritis, psoriasis and spondyloarthritis. This review describes these concepts, shows their interests through clinical observations, and finally discusses strategies to optimize therapeutic strategies.