Recovery from acute lung injury can be regulated via modulation of regulatory T cells and Th17 cells.

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.