Local IL-17 positive T cells are functionally associated with neutrophil infiltration and their development is regulated

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Inflammation Research

ORIGINAL RESEARCH PAPER

Local IL‑17 positive T cells are functionally associated with neutrophil infiltration and their development is regulated by mucosal microenvironment in nasal polyps Sifei Yu1,2   · Chen Cao1 · Qianying Li1 · Xueyi Wen1 · Xuexue Guo1 · Qing Bao1 · Yutao Zhou1 · Liyue Li1 · Xiaoyan Ye1 · Tianying Li1 · Hexin Chen1 · Changyou Wu2 · Chunwei Li1 Received: 5 September 2020 / Revised: 10 November 2020 / Accepted: 12 November 2020 © Springer Nature Switzerland AG 2020

Abstract Objective and design  IL-17 plays essential roles in neutrophilic inflammation in the lower respiratory tract, however, the characteristics of local IL-17+ T cells in nasal inflammatory mucosa are not fully understood. We investigated the roles of IL-17+ T cells in regulating neutrophil infiltration and the effect of the mucosal microenvironment in modulating IL-17+ T cell differentiation in CRSwNP tissues. Subjects  47 polyp tissues from chronic rhinosinusitis with nasal polyps (CRSwNP) patients without corticosteroid therapy and 26 tissues from healthy mucosa were obtained. Methods  Immunohistochemistry and flow cytometry were used to analyze the neutrophil infiltration, local IL-17+ T cell subsets, as well as cytokine producing profiles of IL-17+ T cell; tissue homogenates were used to study neutrophil migration and IL-17+ T cell differentiation. Results  Increase of IL-17+ cells and IL-17+ T cell subsets was significant in polyp tissues versus controls, IL-17+ cell number was positively correlated with neutrophil infiltration; while homogenates from polyp tissues with high IL-17 promoted neutrophil migration in vitro. IL-17 response was found in polyp-derived T cells upon Staphylococcus aureus infection. IL-17+ T cells were also down-regulated in polyps from patients treated with glucocorticoid steroids, and exhibited polyfunctionality patterns in polyp tissues. Finally, IL-17+ T cell differentiation could be induced by IL-23, and homogenates from polyps could enhance IL-17+ T cell development. Conclusions  This study determined a functional association of IL-17+ T cells with neutrophils in CRSwNP, and revealed that polyp microenvironment could promote IL-17+ T cell differentiation, suggesting a potential feedback role for IL-17+ T cell development and local neutrophilic inflammation. Keywords  Chronic rhinosinusitis with nasal polyps · IL-17 · IL-17+ cells · Neutrophils · Mucosal microenvironment

Introduction Responsible Editor: John Di Battista. Sifei Yu and Chen Cao are contributed equally to this work. * Changyou Wu [email protected] * Chunwei Li [email protected] 1



Department of Otolaryngology, Guangzhou Key Laboratory of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China



Institute of Immunology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China

2

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common chronic upper airway inflammation that is often associated with asthma and other airway dise