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Inhibition of Bcl-6 Expression Ameliorates Asthmatic Characteristics in Mice

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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 IgG1 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 IgG1 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.

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Acknowledgments

We thank Dr. Li LIU and Dr. Ling LIU for their assistance during the preparation of this manuscript.

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Author notes

  1. The authors contributed equally to this work.

Authors and Affiliations

  1. Department of Respiratory and Critical Care Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, China

    Chang-zhi Zhou, 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

  2. Department of General Surgery, Wuhan Wuchang Hospital, Wuhan University of Science and Technology, Wuhan, 430063, China

    Xiong Xiong

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  1. Chang-zhi Zhou
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Correspondence to Liang-chao Wang or Shuang Geng.

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Additional information

This research was supported by the National Natural Science Foundation of China (No. 81400020) and a Scientific Research Project of the Wuhan Municipal Health and Family Planning Commission (No. WX19C30).

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Zhou, Cz., Xiong, X., Tan, Wj. et al. Inhibition of Bcl-6 Expression Ameliorates Asthmatic Characteristics in Mice. CURR MED SCI 44, 110–120 (2024). https://doi.org/10.1007/s11596-023-2800-z

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  • DOI: https://doi.org/10.1007/s11596-023-2800-z

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