Diversity and flexibility of Th17 effector functions

IL-17-producing CD4⁺ T-helper cells (Th17 cells) have been recognised as important drivers of pathogenesis in a multitude of inflammatory diseases, including arthritis. The cytokines and transcription factors that instruct and execute Th17 lineage differentiation have been identified. This has induced hopes that targeting Th17 cells might yield a magic bullet against autoimmune diseases. A new wave of published reports shows that matters are more complicated: Th cells can coexpress IL-17 with a variety of other cytokines, including IFNγ, IL-4, or IL-10, with different functional consequences. Moreover, IL-17 memory is not stable - Th17 cells can be instructed to express other lineage-defining cytokines and to halt IL-17 expression. Finally, Th17 cells may exert tissue-protective effects, even in the context of some inflammatory diseases. Manipulating Th17 cells or IL-17 effects may be more difficult than initially appreciated. Notwithstanding these facts, IL-17 remains a valuable and even more interesting therapeutic target.