Acute lung injury (ALI) is a severe inflammatory disease, for which no specific treatment exists. The decreased ratio of regulatory T cells (CD4+ CD25+ FoxP3 Tregs) and Th17 cells is implicated in ALI and inflammation. We here investigated whether maintaining the balance of CD4+ CD25+ Foxp3+ Tregs and Th17 cells can alleviate lung injury. For CD4+ CD25+ FoxP3 Treg depletion, 200 μg of an anti-CD25 antibody was administered intraperitoneally per mouse on days -3 and -1 before lipopolysaccharide (LPS) instillation. And 150 μg of TGF-β was administered intraperitoneally per mouse on day 0 after LPS instillation. To down-regulate of Th17 cells, 200 μg per mouse of isotype, IL-17 or IL-22 antibodies were injected intraperitoneally into mice at days 0 after LPS instillation. We detected lung morphology; lung wet-to-dry weight ratio; protein concentration, the count of total cells, neutrophils and macrophages, and cytokines in bronchoalveolar lavage fluid (BALF). And we also evaluated the percentage of CD4+ CD25+ Foxp3+ Tregs in lung, and Th17 cells in lung. CD4+ CD25+ Foxp3+ Tregs depletion via anti-CD25 treatment or TGF-β neutralization delayed recovery of ALI. The prolonged inflammation was mainly dominated by neutrophils, macrophages and Th17 cells. Furthermore, inhibition of Th17 cells via monoclonal antibodies against IL-17 and IL-22 alleviated ALI inflammation by inhibiting the recruitment of neutrophils and macrophages, increasing the number of CD4+ CD25+ Foxp3+ Tregs. Our findings support a critical role for CD4+ CD25+ Foxp3+ Tregs in regulating from ALI pathophysiology, and a potential therapeutic role for the inhibition of Th17 cells in ALI treatment. These findings provide a rationale for treating patients with ALI by modulating CD4+ CD25+ Foxp3+ Tregs and Th17 cells.
Keywords: Th17 cells; acute lung injury; disease resolution; inflammation; regulatory T cells.
© 2018 The Foundation for the Scandinavian Journal of Immunology.