This study examines the role of interleukin 23 (IL-23) in airway inflammation in asthma, focusing on the ability of IL-23 to promote inflammation independently of the known IL-17 pathway and via its effect on T helper 2 (Th2) polarisation. These interactions are studied using in vitro and in vivo techniques.

Mice exposed to allergen showed a significant increase in IL-23-specific p19 mRNA and IL-23 receptor mRNA. In mice induced to overexpress IL-23, an increased inflammatory cell infiltrate was observed after allergen challenge. In IL-23 knockout mice, exposure to the same allergen challenge resulted in a significant reduction in airway inflammation.

Having established a role for IL-23 in airway inflammation the authors next examined its signalling pathway. No significant alteration in IL-17 expression was seen between the IL-23 knockout and IL-23-expressing mice, thus suggesting a possible pathway independent of IL-17. In contrast, the levels of Th2 cytokines (IL-4, IL-5 and IL-13) were seen to vary significantly between the two groups. In the knockout mice, a dramatic reduction in Th2 cytokines was observed in lymphatic cultures.

Further examination of this pathway in vitro used CD4 T cells activated via an antigen-presenting cell-dependent or -independent mechanism. In both cases IL-23 affected Th2 differentiation. Partial Th2 inhibition was seen in the absence of IL-23 and increasing differentiation was observed in the IL-23-positive cell line.

This study confirms the importance of IL-23 and its receptor in regulating airway inflammation and identifies a possible signalling pathway between IL-23 and Th2 cells independent of IL-17.

▶ Peng J, Yang XO, Tesfaigzi Y, Chang SH et al. IL-23 signalling enhances Th2 polarization and regulates allergic airway inflammation, lung function, and COPD in high-risk populations. Cell Res 2010;20:62–71.