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

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.

Serum CXCL9 and CCL17 as biomarkers of declining pulmonary function in chronic bird-related hypersensitivity pneumonitis

“…IFN-gamma resulted in an increase in CXCL9 mRNA expression by human alveolar epithelial type II or A549 cells [28]. In our previous study, we demonstrated that IL-17A and neutrophils were crucial for the development of pulmonary inflammation in murine models of acute HP [29]. Those inflammatory responses may contribute to CXCL9 production in HP patients.…”

A dendritic cell-based systemic vaccine induces long-lived lung-resident memory Th17 cells and ameliorates pulmonary mycosis

“…Because populations of Siglec-F high Ly6G low SSC high eosinophils and alveolar macrophages were detected outside of the neutrophilgate, neutrophils expressing Siglec-F and CD11c were clearly distinguishable from other cells. Previous studies have shown that a subpopulation of activated neutrophils expressed Siglec-F and CD11c on the cell surface [21][22][23][24][25] . Siglec-F is known to be an inhibitory receptor that can be expressed in activated lung T cells as well as eosinophils 26 .…”

“…Previous studies suggest that neutrophils are required for the induction of multinucleated giant cells (MGCs) that can suppress the growth of Mycobacterium tuberculosis 27 . IL-17A-dependent granuloma formation is also known in murine tuberculosis 28 , cryptococcosis 29 , and hypersensitivity pneumonitis models 25 . Our previous study showed that MGC formation was correlated with protective response against pulmonary infection with highly virulent C. gattii 7 .…”

Diagnosis and Treatment of Fibrotic Hypersensitivity Pneumonia. Where We Stand and Where We Need to Go

“…Human and animal studies suggest that reduced number or function of gd T cells (important in immune response attenuation) is associated with fibrosis in HP (38,68,69). IL-17A may be important, with reduced inflammation and less collagen formation when IL-17 is absent or neutralized (70)(71)(72). Neutrophils are implicated as the source of IL-17 (70), and are correlated with the extent of fibrosis in human fibrotic HP lungs (73).…”