Inhibition of Bcl-6 exp­ression ameliorates asthmatic characteristics in mice

Background: Bcl-6 is an essential factor control Tfh cells differentiation. T lymphocytes assistance B lymphocytes regulate IgE secretion is a crucial part of asthma. However, Bcl-6 direct effect on asthmatic characteristics, such as IgE secretion is unknown. Methods: We adopted OVA-induced BALB/c mice, and Bcl-6 small interfering RNA to inhibit Bcl-6 expression. There were five groups: Control, Blank carrier, Asthma, Bcl-6 siRNA interference, and DXM-treated. Then mice were euthanized, collected lungs tissues, peripheral blood, lymph nodes and spleen. Histopathological diagnosis, AR and LC of each group were detected. Expression levels of surface molecular markers on Tfh cells in pre-mentioned tissues were examined by FCM. Bcl-6 mRNA expression was detected by RT-PCR, and Bcl-6 protein grayscale was detected by Western-blot. Finally, the concentration of IgE and IgG 1 in peripheral blood and BALF were detected, and correlation analysis with the Tfh cells ratio in counterparts was applied. Results: Typical pathological changes were observed in lung tissue of asthmatic mice, that was alleviated by Bcl-6 antagonism and DXM. Asthmatic ones had increased AR and decreased LC, while Bcl-6 siRNA interference or DXM treatment could reduce AR and improve LC. FCM indicated that Tfh cells ratio in peripheral blood, lymph nodes, and spleen of asthmatic mice increased significantly comparing to control ones, and that also decreased significantly after Bcl-6 siRNA interferencing and DXM treatment. The trend occured in eosinophils ratio of BALF. Applying RT-PCR accessed the Bcl-6 mRNA expression in PBMCs, which was significantly higher of asthmatic mice than control ones. Whereas that was significantly decreased when Bcl-6 inhibited and DXM treated. Bcl-6 protein expression was similar to that of mRNA expression in Western-blot. As well as the IgE secretion in serum and BALF, B cells expression in PBMCs have the same trend. Besides, in asthmatic mice, the Tfh cells ratio in peripheral blood was strong positively correlated with the level of IgE in serum and BALF, but not that of IgG 1 . Conclusions: Inhibition of Bcl-6 expression can ameliorate airway inflammation and airway hyper-responsiveness in asthmatic mice by blocking Tfh cell differentiation, which concomitantly reduces B cells regulation IgE production.