17 and 23

The discovery of the cytokine IL-17 more than 10 yr ago1 paved the way for the recent identification of a distinct subset of helper T cells producing IL-17 (Th17 cells). This novel proinflammatory class of Th cells2 disrupts the Th1/Th2 paradigm that had shaped our view of the immune system and immune-mediated disease for more than 20 yr.3 Th1 cells, regulated by the transcription factor T-bet and characterized by the production of IFN-γ and IL-12, provide defense against viruses and intracellular pathogens and are associated with autoimmunity, whereas Th2 cells, modulated by GATA-3 and producing IL-4 and IL-13, provide immunity against extracellular parasites and play a role in the promotion of allergy. The novel Th17 cells represent a third distinct lineage of helper CD4+ T cells that are regulated by a specific transcription factor, RoR-γt,4 and produce IL-17. IL-17 possesses pleiotropic effects,5 including release of proinflammatory cytokines (TNF-α, IL-6, and IL-8), upregulation of adhesion and MHC molecules, and recruitment of monocytes and neutrophils.Th17 cells in mice develop from naive CD4+ cells in the presence of TGF-β and IL-6; however, in humans, unraveling their pathway to differentiation is more complex. Initially, Th17 differentiation was thought to be driven by IL-1 and enhanced by IL-6 and IL-23.6,7 More recently, TGF-β and IL-21 also seem integral for their differentiation in humans.8 Significantly, IL-23 is a cytokine …