Dual Role of Th17 Cytokines, IL-17A,F, and IL-22 in Allergic Asthma

The proinflammatory role of T helper (Th) 17 cells and therefore of its cytokines, IL-17 (IL-17A), IL-17F, and IL-22, in autoimmune disorders has been favored, although there is evidence that not only IL-17A but also IL-17F and IL-22 have a dual role as negative regulators. Here we review the concept of the dual function of IL-17A, IL-17F, and IL-22 in the light of recent strategies to use neutralization of these cytokines as potential alternative to neutralizing TNF and IL-1 treatments in chronic inflammatory disorders. Expectedly, in allergic lung inflammation, neutralization of IL-17A inhibited neutrophil recruitment. However, this IL-17A antibody treatment concomitantly increased eosinophil recruitment by neutralizing IL-17A’s dual role as negative regulator. IL-17A negatively regulated dendritic cell function and activation of T helper cell (Th)2 cytokine production. Furthermore, IL-17A inhibited Th2-characteristic chemokine and adhesion molecule expression. On a mechanistic level, IL-17A acted on IκB-β by preventing degradation and in turn leading to reduced NF-κB activation or IL-17A inhibited transcription factor IRF-1. Therefore, anti-IL-17A therapy, although presenting a promising lead in chronic inflammatory disorders, bears a potential risk of exacerbating allergic asthma.