Cross-talk between T_H2 and T_H17 pathways in patients with chronic rhinosinusitis with nasal polyps.

Abstract

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease with a spectrum of endotypes. T_H2- and T_H17-related cytokines are 2 central regulators involved in the inflammation associated with CRSwNP. We sought to investigate the interregulation of T_H2 and T_H17 pathways in Chinese patients with CRSwNP. Levels of key T_H2- and T_H17-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_H2 and T_H17 cytokines and the effects of dexamethasone treatment were studied in dispersed nasal polyp cells. Associations between T_H2- and T_H17 related factors and comorbid atopic status and asthma, disease recurrence, and edema scores were also explored. Four CRSwNP groups were classified based on expression or nonexpression of mutually exclusive T_H2- and T_H17-related factors. The T_H2 cytokines IL-4 and IL-13 inhibited expression of T_H17-related factors, whereas the T_H17 cytokines IL-17 and TGF-β1 enhanced expression of T_H2-related factors. Dexamethasone treatment inhibited both the T_H2 and T_H17 pathways. A patient's atopic status was related to their T_H2 immune response. Edema scores were positively correlated with the T_H2 pathway and negatively correlated with the T_H17 pathway. The T_H2 and T_H17 pathways are mutually exclusive and regulate each other, favoring the development of a T_H2 immune response in Chinese patients with CRSwNP.