Diversity and flexibility of Th17 effector functions.docVIP

Kamradt and Chang Arthritis Research Therapy 2011,13:106 /content/13/2/106 COMMENTARY Diversity and ? exibility of Th17 e? ector functions Thomas Kamradt * and Hyun-Dong Chang 1 2 17 cells were originally characterised by their co- expres sion of IL-17 (also called IL-17A) together with IL-17F, TNFα, granulocyte–macrophage colony-stimu- Abstract IL-17-producing CD4 T-helper cells (Th17 cells) have + been recognised as important drivers of pathogenesis in a multitude of in?ammatory diseases, including arthritis. The cytokines and transcription factors that instruct and execute Th17 lineage di?erentiation have been identi?ed. 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 di?erent functional consequences. Moreover, IL-17 memory is not stable – Th17 cells can be instructed to express other lineage-de?ning cytokines and to halt IL-17 expression. Finally, Th17 cells may exert tissue- protective e?ects, even in the context of some in?ammatory diseases. Manipulating Th17 cells or IL-17 e?ects may be more di?cult than initially appreciated. Notwithstanding these facts, IL-17 remains a valuable and even more interesting therapeutic target. lat ing factor, and lymphotac 2 cyto- kines [3,4]. Over the past several years it has become clear that 17 cells do not represent a homo geneous lineage. IL-17 can be coexpressed with a variety of other cytokines including IL-21, IL-22, IFNγ, IL-10, and IL-4, with consequences for the cells’ functionality [1,2,5-7]. Moreover, IL-17 is not exclusively produced by CD4 cells but also by CD8 T cells, γδ T cells, natural killer T + + cells, natural killer cells, and perhaps also