Interleukin-17A and Neutrophils in a Murine Model of Bird-Related Hypersensitivity Pneumonitis.

Masahiro Ishizuka,Kozo Suhara,Makito Yasui,Yasunari Miyazaki,Tomoya Tateishi,Masahiro Masuo,Naohiko Inase,Samithamby Jeyaseelan

doi:10.1371/journal.pone.0137978

Masahiro Ishizuka, Kozo Suhara + Show 6 more

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https://doi.org/10.1371/journal.pone.0137978

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Journal: PloS one	Publication Date: Sep 14, 2015
Citations: 16	License type: CC BY 4.0

Affiliation: Tokyo Medical and Dental University

Abstract

Hypersensitivity pneumonitis (HP) is an immune mediated lung disease induced by the repeated inhalation of a wide variety of antigens. Bird-related hypersensitivity pneumonitis (BRHP) is one of the most common forms of HP in human and results from the inhalation of avian antigens. The findings of a recent clinical analysis suggest that in addition to Th1 factors, the levels of interleukin(IL)-17 and IL-17-associated transcripts are increased in the setting of HP, and that both IL-17A and neutrophils are crucial for the development of pulmonary inflammation in murine models of HP. Our objectives were to investigate the roles of IL-17A and neutrophils in granuloma-forming inflammation in an acute HP model. We developed a mouse model of acute BRHP using pigeon dropping extract. We evaluated the process of granuloma formation and the roles of both IL-17A and neutrophils in a model. We found that the neutralization of IL-17A by the antibody attenuated granuloma formation and the recruitment of neutrophils, and also decreased the expression level of chemokine(C-X-C motif) ligand 5 (CXCL5) in the acute HP model. We confirmed that most of the neutrophils in the acute HP model exhibited immunoreactivity to the anti-IL-17 antibody. We have identified the central roles of both IL-17A and neutrophils in the pathogenesis of granuloma formation in acute HP. We have also assumed that neutrophils are an important source of IL-17A in an acute HP model, and that the IL-17A-CXCL5 pathway may be responsible for the recruitment of neutrophils.

Highlights

Hypersensitivity pneumonitis (HP) is an immune mediated lung disease induced by the inhalation of a wide variety of antigens [1]
In the pigeon dropping extract (PDE)-challenged mice, granulomata composed of lymphocytes, macrophages and granulocytes were noted in the peribronchiolar and perivascular areas, and many segmented granulocytes were observed in the perivascular areas, in particular (Fig 2)
The repeated exposure to the PDE antigen in our model of HP resulted in the marked infiltration of inflammatory cells and the formation of granulomata composed of lymphocytes, macrophages and segmented granulocytes in the peribronchiolar and perivascular areas (Fig 2B)

Summary

Introduction

Hypersensitivity pneumonitis (HP) is an immune mediated lung disease induced by the inhalation of a wide variety of antigens [1]. Bird-related hypersensitivity pneumonitis (BRHP) is one of the most common forms of HP and results from the inhalation of avian antigens [2]. The presence of specific-IgG antibodies in most cases of HP suggests that a type III hypersensitivity mechanism may be responsible for the disease’s underlying pathology. A type III hypersensitivity mechanism has been pathophysiologically proposed, it is currently believed that a type IV hypersensitivity mechanism mediated by T cells may be involved [3].

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