Imbalance of Th17/Treg in the Pathogenesis of Mice with Paraquat-induced Acute Lung Injury
AbstractRecent studies suggest that imbalances in the ratios of CD4+ T helper cell subsets, T helper-17 (Th17) and regulatory T (Treg) cells play a crucial role in the pathogenesis of acute lung injury (ALI). However, studies of the imbalance of Th17/Treg in paraquat (PQ)-induced ALI have not been reported. Therefore, we investigated whether the ratio of Th17/Treg cells in a mouse model of PQ-induced ALI contributes to pathogenesis of ALI. Male Kunming mice were randomly treated with saline (control group) or PQ (PQ-poisoned (PQP) group); mice were sacrificed at either 12 hours (PQP-12h) or 24 hours (PQP-24h and control) post-treatment. Hematoxylin-eosin and TUNEL staining procedures were performed to examine inflammation and apoptosis. The presence of Th17 and Treg cells was measured by flow cytometry; the expression of putative Th17 cytokines and transcription factors was measured by ELISA and western blot analysis. Compared with control mice, lung inflammation and apoptosis were dramatically increased in PQP mice at 12 and 24 hours after poisoning. In addition, poisoned mice displayed significant increases in the presence of CD4+IL-17+ T cells (Th17) and in the expression of IL-17A and IL-17, as measured by flow cytometry and western blot assays. This increase was most notable after 24 hours of PQ exposure. Furthermore, poisoned mice displayed marked decreases in the presence of CD4+CD25+Foxp3+ T cells (Treg) and in the expression of IL-35 and the transcription factor Foxp3. These results suggest that an imbalanced ratio of Th17/Treg cells may contribute to the pathogenesis of PQ-induced ALI.
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