Oncotarget

Research Papers: Immunology:

Neutralization of interleukin-17 suppresses allergic rhinitis symptoms by downregulating Th2 and Th17 responses and upregulating the Treg response

Zhao Wei Gu, Yun Xiu Wang and Zhi Wei Cao _

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Oncotarget. 2017; 8:22361-22369. https://doi.org/10.18632/oncotarget.15652

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Abstract

Zhao Wei Gu1,*, Yun Xiu Wang2,* and Zhi Wei Cao1

1 Department of Otorhinolaryngology, China Medical University Affiliated Shengjing Hospital, Shenyang, Liaoning, China

2 Department of Medical Insurance, China Medical University Affiliated Shengjing Hospital, Shenyang, Liaoning, China

* Co-first authors

Correspondence to:

Zhi Wei Cao, email:

Keywords: interleukin-17, neutralization, Th2, Th17, allergic rhinitis, Immunology and Microbiology Section, Immune response, Immunity

Received: March 02, 2016 Accepted: February 15, 2017 Published: March 01, 2017

Abstract

Allergic rhinitis (AR) has long been considered to predominantly involve the actions of Th2 cells, with relatively small contributions from Th1 cells. In recent years, the discovery of Th17 and regulatory T (Treg) cells has rendered the Th1/Th2 balance paradigm more complex and expanded our understanding of the pathogenesis of AR. IL-17, a key cytokine produced by Th17 cells, is known to induce allergen-specific Th2 cell activation, eosinophil and neutrophil accumulation, and serum IgE production in asthma; all of these features may play important roles in AR. To the best of our knowledge, only a few studies have assessed the feasibility of using IL-17 antagonists to treat AR. Thus, the principal objectives of the present study were, first, to determine the status of Th17 and Treg cells in the nasal mucosa of a mouse model of AR, and, second, to investigate the effects of IL-17 on such cells and the therapeutic efficacy of anti-IL-17 antibodies (Abs) in the context of AR. Anti-IL-17 Abs were given intranasally during the re-challenge of BALB/c mice with ovalbumin (OVA)-induced AR. We measured the numbers of nasal rubbing motions and sneezes, eosinophil and neutrophil levels, Th1, Th2, Th17, and Treg parameters in the nasal mucosa. Anti-IL-17 Abs markedly reduced the number of nasal rubbing motions and sneezes, decreased eosinophil and neutrophil infiltration, reduced Th2 and Th17 responses, and increased the Treg response. Anti-IL-17 Ab treatment protects against AR. These results will improve our understanding of AR pathogenesis and may lead to the development of novel therapeutic approaches for management of the condition.


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