Recurrent airway obstruction, Th17 and IL-26

Recurrent airway obstruction occurs in several mammals including humans and horses. Evolving evidence suggests a number of different endotypes of this condition, frequently referred to as asthma in humans. These endotypes are signified by different types of inflammatory events associated with more or less specific clinical phenotypes. The most well-characterized of these endotypes in humans displays T helper cell (Th) 2 activity associated with eosinophilic inflammation and a clinical phenotype that frequently responds well to inhaled glucocorticoids. A less well-characterized endotype in humans displays Th17 activity associated with neutrophilic inflammation and a clinical phenotype with highly variable airway obstruction and relatively poor sensitivity to inhaled glucocorticoids. So far, the latter endotype has been assessed mainly as cytokine signaling via the archetype Th17 cytokine interleukin (IL)-17A and there is data from horses along these lines as well. Given that IL-26, although in a different manner compared with IL-17A, exerts effects on the mobilization of neutrophils, it can be anticipated that airway disorders diplaying an excess of these innate effector cells may also involve IL-26. In line with this, recently published evidence suggests that the Th17 cytokine IL-26 is involved in pulmonary host defence as well as in asthma among humans. However, one published report suggests that the IL-26 gene is inactivated in certain mammals including horses. Collectively, the reviewed evidence forwards a rationale for targeting IL-17A in reversible airway obstruction of both humans and horses. In contrast, the corresponding rationale for targeting IL-26 may be restricted to humans. Further study of these therapeutic approaches is warranted.