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

Min Wang; Nan Zhang; Ming Zheng; Ying Li; Lingling Meng; Yu Ruan; Jinbo Han; Na Zhao; Xiangdong Wang; Luo Zhang; Claus Bachert

doi:10.1016/j.jaci.2019.06.023

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

J Allergy Clin Immunol. 2019 Nov;144(5):1254-1264. doi: 10.1016/j.jaci.2019.06.023. Epub 2019 Jul 2.

Authors

Min Wang¹, Nan Zhang², Ming Zheng³, Ying Li⁴, Lingling Meng⁵, Yu Ruan⁴, Jinbo Han¹, Na Zhao⁶, Xiangdong Wang⁷, Luo Zhang⁸, Claus Bachert⁹

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China.
² Upper Airways Research Laboratory, Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent, Belgium.
³ Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
⁴ Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China.
⁵ Department of Otolaryngology, Bayan Nur Hospital, Bayan Nur, China.
⁶ Department of Otolaryngology, Yanqing District Hospital, General Practice and Continuing Education Capital Medical University, Beijing, China.
⁷ Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China; Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China. Electronic address: entwxd@vip.sina.com.
⁸ Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China; Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China. Electronic address: dr.luozhang@139.com.
⁹ Upper Airways Research Laboratory, Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent, Belgium; Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institute, Stockholm, Sweden; Department of Ear, Nose and Throat Diseases, Karolinska University Hospital, Stockholm, Sweden.

PMID: 31271788
DOI: 10.1016/j.jaci.2019.06.023

Abstract

Background: 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.

Objective: We sought to investigate the interregulation of T_H2 and T_H17 pathways in Chinese patients with CRSwNP.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Chronic rhinosinusitis with nasal polyps; T(H)17; T(H)2; endotypes; shift.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Cells, Cultured
Chronic Disease
Female
Humans
Interleukin-17 / metabolism
Interleukin-5 / metabolism
Male
Middle Aged
Nasal Polyps / immunology*
Paracrine Communication
Rhinitis / immunology*
Sinusitis / immunology*
Th17 Cells / immunology*
Th2 Cells / immunology*

Substances

Interleukin-17
Interleukin-5