Blocking IL-17a Signaling Decreases Lung Inflammation and Improves Alveolarization in Experimental Bronchopulmonary Dysplasia

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of preterm infants that is associated with life-long morbidities. Inflammatory insults contribute to BPD pathogenesis. Although the proinflammatory cytokine, IL-17a, plays a role in various neonatal inflammatory disorders, its role in BPD pathogenesis is unclear. To test the hypothesis that blocking IL-17a signaling decreases lipopolysaccharide (LPS)–mediated experimental BPD in neonatal mice, wild-type mice were injected intraperitoneally with phosphate-buffered saline or LPS during the saccular lung developmental phase. Pulmonary IL-17a expression was determined by enzyme-linked immunosorbent assay and by flow cytometry. LPS-injected mice had higher pulmonary IL-17a protein levels and IL-17a⁺ and IL-22⁺ cells. γδ T cells, followed by non–T lymphoid cells, were the primary producers of IL-17a. Wild-type mice were then injected intraperitoneally with isotype antibody (Ab) or IL-17a Ab, while they were treated with phosphate-buffered saline or LPS, followed by quantification of lung inflammatory markers, alveolarization, vascularization, cell proliferation, and apoptosis. LPS-mediated alveolar simplification, apoptosis, and cell proliferation inhibition were significantly greater in mice treated with isotype Ab than in those treated with IL-17a Ab. Furthermore, STAT1 activation and IL-6 levels were significantly greater in LPS-exposed mice treated with isotype Ab than in those treated with IL-17a Ab. The study results indicate that blocking IL-17a signaling decreases LPS-mediated experimental BPD.