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