The role of interleukin-17 in asthma: a protective response?

While there now exist effective treatments for type 2 high, eosinophilic asthma, there are no specific therapies for 40-50% of people with asthma with other phenotypes, which result from poorly understood underlying pathological mechanisms. One such pathology is neutrophilic inflammation, which has been associated with interleukin (IL)-17 family cytokines. Human genetic studies identified IL-17 polymorphisms associated with asthma; in murine models of allergic airways disease, IL-17A contributes to airway hyperresponsiveness, and in humans, elevated airway IL-17A levels are repeatedly observed in severe asthma. However, the directionality of this association is unknown, and the assumption that IL-17 cytokines drive disease pathology remains speculative. Here, we explore the evidence underlying the relationship between IL-17 and asthma, we review lessons learned from investigating IL-17 in other inflammatory diseases, and discuss the possibility that IL-17 may even be protective in asthma rather than pathogenic. We also critically examine the newly proposed paradigm of a reciprocal relationship between type 2 and type 17 airways inflammation. In summary, we suggest an association between IL-17 and asthma, but research is needed examining the diverse functions of these cytokines, their longitudinal stability, their response to clinical interventions, and for mechanistic studies determining whether they are protective or pathogenic.