IL-17A is essential to the development of elastase-induced pulmonary inflammation and emphysema in mice

Etsuko Kurimoto,Yoichiro Iwakura,Erwin W Gelfand,Mikio Kataoka,Yasushi Tanimoto,Mitsune Tanimoto,Koichi Waseda,Genyo Ikeda,Nobuaki Miyahara,Akihiko Taniguchi,Hisakazu Nishimori,Hikari Koga,Arihiko Kanehiro

doi:10.1186/1465-9921-14-5

Abstract

BackgroundPulmonary emphysema is characterized by alveolar destruction and persistent inflammation of the airways. Although IL-17A contributes to many chronic inflammatory diseases, it’s role in the inflammatory response of elastase-induced emphysema remains unclear.MethodsIn a model of elastase-induced pulmonary emphysema we examined the response of IL-17A-deficient mice, monitoring airway inflammation, static compliance, lung histology and levels of neutrophil-related chemokine and pro-inflammatory cytokines in bronchoalveolar lavage (BAL) fluid.ResultsWild-type mice developed emphysematous changes in the lung tissue on day 21 after elastase treatment, whereas emphysematous changes were decreased in IL-17A-deficient mice compared to wild-type mice. Neutrophilia in BAL fluid, seen in elastase-treated wild-type mice, was reduced in elastase-treated IL-17A-deficient mice on day 4, associated with decreased levels of KC, MIP-2 and IL-1 beta. Elastase-treated wild-type mice showed increased IL-17A levels as well as increased numbers of IL-17A+ CD4 T cells in the lung in the initial period following elastase treatment.ConclusionsThese data identify the important contribution of IL-17A in the development of elastase-induced pulmonary inflammation and emphysema. Targeting IL-17A in emphysema may be a potential therapeutic strategy for delaying disease progression.

Highlights

Pulmonary emphysema is characterized by alveolar destruction and persistent inflammation of the airways
Development of emphysema is reduced in IL-17A−/− mice To elucidate the role of IL-17A in the development of emphysema, we examined lung function 21 days following porcine pancreatic elastase (PPE) treatment
We have shown that neutrophil-related chemokines such as keratinocyte-derived chemokine (KC) and macrophage inflammatory protein 2 (MIP-2) were increased at a relatively early stage following elastase treatment, which was associated with increased levels of IL-17A, and increased numbers of neutrophils in the airways, suggesting an important role for IL-17A in the recruitment of neutrophils at a relatively early stage

Summary

Introduction

Pulmonary emphysema is characterized by alveolar destruction and persistent inflammation of the airways. It has been reported that there are increased numbers of tertiary lymphoid follicles in the lungs of patients with COPD [3,4], and that these follicles are organized structures with a B-cell core, T cells in the periphery, and dendritic cells capable of antigen presentation [5,6,7]. IL-17A and IL-17 F display high sequence homology and can be secreted as homodimers, as well as IL-17A/F heterodimers, by both mouse and human cells [11] These cytokines are produced by a subset of CD4+ lymphocytes known as T-helper (Th) 17 cells [12] and contribute to the development of autoimmune disease [13,14]. IL-17A has been shown to induce the production of chemokines and inflammatory cytokines such as keratinocyte-derived chemokine (KC), macrophage inflammatory protein 2 (MIP-2), and IL-1β, that promote neutrophilic inflammation [15,16,17]

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