Cross-talk between TH2 and TH17 pathways in patients with chronic rhinosinusitis with nasal polyps

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease with a spectrum of endotypes. T(H)2- and T(H)17-related cytokines are 2 central regulators involved in the inflammation associated with CRSwNP. Objective: We sought to investigate the interregulation of T(H)2 and T(H)17 pathways in Chinese patients with CRSwNP. Methods: Levels of key T(H)2- and T(H)17-related factors were measured in homogenates of polyp tissue obtained from patients with CRSwNP. The relationship of these factors and their expression in groups classified according to tissue IL-5 and IL-17 concentrations were analyzed. Cross-regulation of T(H)2 and T(H)17 cytokines and the effects of dexamethasone treatment were studied in dispersed nasal polyp cells. Associations between T(H)2- and T(H)17 related factors and comorbid atopic status and asthma, disease recurrence, and edema scores were also explored. Results: Four CRSwNP groups were classified based on expression or nonexpression of mutually exclusive T(H)2- and T(H)17-related factors. The T(H)2 cytokines IL-4 and IL-13 inhibited expression of T(H)17-related factors, whereas the T(H)17 cytokines IL-17 and TGF-beta 1 enhanced expression of T(H)2-related factors. Dexamethasone treatment inhibited both the T(H)2 and T(H)17 pathways. A patient's atopic status was related to their T(H)2 immune response. Edema scores were positively correlated with the T(H)2 pathway and negatively correlated with the T(H)17 pathway. Conclusion: The T(H)2 and T(H)17 pathways are mutually exclusive and regulate each other, favoring the development of a T(H)2 immune response in Chinese patients with CRSwNP.