Inhibition of Bcl-6 Expression Ameliorates Asthmatic Characteristics in Mice

Chang-zhi Zhou1(), Xiong Xiong2(), Wei-jun Tan1, Ya-fei Wang1, Zhen Yang1, Xue-ying Li1, Xiu-wen Yang1, Xiao-fan Liu1, Sun-feng Yu1, Liang-chao Wang1(), Shuang Geng1()

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Current Medical Science ›› 2024, Vol. 44 ›› Issue (1) : 110-120. DOI: 10.1007/s11596-023-2800-z

Inhibition of Bcl-6 Expression Ameliorates Asthmatic Characteristics in Mice

  • Chang-zhi Zhou1(), Xiong Xiong2(), Wei-jun Tan1, Ya-fei Wang1, Zhen Yang1, Xue-ying Li1, Xiu-wen Yang1, Xiao-fan Liu1, Sun-feng Yu1, Liang-chao Wang1(), Shuang Geng1()
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Abstract

Abstract
Objective

The function of Bcl-6 in T follicular helper (Tfh) cell maturation is indispensable, and Tfh cells play a pivotal role in asthma. This study investigated the impact of Bcl-6 on asthmatic traits.

Methods

The microscopic pathological alterations, airway resistance (AR), and lung compliance (LC) were determined in asthmatic mice and Bcl-6 interference mice. The surface molecular markers of Tfh cells and the Bcl-6 mRNA and protein expression were determined by flow cytometry, RT-qPCR, and Western blotting, respectively. The relationships between the Tfh cell ratio and the IgE and IgG 1 concentrations in peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage fluid (BALF) were determined.

Results

Asthmatic inflammatory changes were observed in the lung tissue and were attenuated by Bcl-6 siRNA and dexamethasone (DXM). Asthmatic mice exhibited an increased AR and a decreased LC, while Bcl-6 siRNA or DXM mitigated these changes. The percentages of Tfh cells and eosinophils were significantly increased in the asthmatic mice, and they significantly decreased after Bcl-6 inhibition or DXM treatment. RT-qPCR and Western blotting analyses revealed that the Bcl-6 expression level in PBMCs was significantly higher in asthmatic mice, and it decreased following Bcl-6 inhibition or DXM treatment. The IgE expression in the serum and BALF and the B cell expression in PBMCs exhibited a similar trend. In asthmatic mice, the ratio of Tfh cells in the peripheral blood showed a strong positive correlation with the IgE levels in the serum and BALF, but not with the IgG 1 levels.

Conclusion

The amelioration of airway inflammation and airway hyper-responsiveness is achieved through Bcl-6 suppression, which effectively hinders Tfh cell differentiation, ultimately resulting in a concurrent reduction in IgE production.

Keywords

Bcl-6 / Tfh / asthma / airway hyper-responsiveness / mouse model

Cite this article

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Chang-zhi Zhou, Xiong Xiong, Wei-jun Tan, Ya-fei Wang, Zhen Yang, Xue-ying Li, Xiu-wen Yang, Xiao-fan Liu, Sun-feng Yu, Liang-chao Wang, Shuang Geng. Inhibition of Bcl-6 Expression Ameliorates Asthmatic Characteristics in Mice. Current Medical Science, 2024, 44(1): 110‒120 https://doi.org/10.1007/s11596-023-2800-z

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