Th17-Associated Cytokines as a Therapeutic Target for Steroid-Insensitive Asthma

Figure 1

Targeting the Th17 pathway. Helper T (Th) 17 cells are derived from naïve CD4⁺ T cells under the control of transforming growth factor (TGF)-𝛽, interleukin (IL)-6, and IL-23 during stimulation by cognate antigen. These cytokines also stimulate Th 17 cells to produce IL-21, which affects Th17 cells themselves to activate a specific transcription factor, RORγt through autocrine regulation. Other proinflammatory cytokines, IL-1𝛽 and tumor necrosis factor (TNF)-α, may also promote Th17 development. RORγt regulates both Th17 cell differentiation and production of Th17-signature cytokines, IL-17A, IL-17F, IL-21, and IL-22. Among these cytokines, IL-17A and IL-17F play pivotal roles in the pathogenesis of asthma and share a common receptor subunit, IL-17 receptor A (IL-17RA), and IL-17 receptor C (IL-17RC). Several inhibitors of Th17 pathway are currently under clinical investigation. G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte macrophage colony-stimulating factor; IL-1R, IL-1 receptor; IL-6R, IL-6 receptor, Treg, regulatory T.