Context
Modified BuShenYiQi formula (M-BYF) is derived from BuShenYiQi formula, used for the treatment of allergic asthma. The exact effect and mechanism of M-BYF on the improvement of asthma remain unclear.
Objective
We investigated the mechanism underlying the therapeutic effect of M-BYF on allergic asthma.
Materials and methods
The asthma model was established in female BALB/c mice that were sensitized and challenged with ovalbumin (OVA). Mice in the treated groups were orally treated once a day with M-BYF (7, 14 and 28 g/kg/d) or dexamethasone before OVA challenge. Control and Model group received saline. Pathophysiological abnormalities and percentages of lung type 2 innate lymphoid cells (ILC2s) and Th9 cells were measured. Expression levels of type 2 cytokines and transcription factors required for these cells function and differentiation were analysed. Expression of vasoactive intestinal polypeptide (VIP)–VPAC2 signalling pathway-related proteins, and percentages of VIP expressing (VIP
+
) cells and VPAC2, CD90 co-expressing (VPAC2
+
CD90
+
) cells were detected.
Results
M-BYF alleviated airway hyperresponsiveness, inflammation, mucus hypersecretion and collagen deposition in asthmatic mice. M-BYF down-regulated percentages of ILC2s and Th9 cells with lower expression of GATA3, PU.1 and IRF4, reduced IL-5, IL-13, IL-9 and VIP production. The decrease in the expression of VIP–VPAC2 signalling pathway and percentages of VIP
+
cells, VPAC2
+
CD90
+
cells were observed after M-BYF treatment. The LD
50
value of M-BYF was higher than 90 g/kg.
Discussion and conclusions
M-BYF alleviated experimental asthma by negatively regulating ILC2s and Th9 cells and the VIP–VPAC2 signalling pathway. These findings provide the theoretical basis for future research of M-BYF in asthma patient population.
CD4+T helper (Th) cells are important mediators of immune responses in asthma and cancer. When counteracted by different classes of pathogens, naïve CD4+T cells undergo programmed differentiation into distinct types of Th cells. Th cells orchestrate antigen-specific immune responses upon their clonal T-cell receptor (TCR) interaction with the appropriate peptide antigen presented on MHC class II molecules expressed by antigen-presenting cells (APCs). T helper 9 (Th9) cells and regulatory T (Treg) cells and their corresponding cytokines have critical roles in tumor and allergic immunity. In the context of asthma and cancer, the dynamic internal microenvironment, along with chronic inflammatory stimuli, influences development, differentiation, and function of Th9 cells and Treg cells. Furthermore, the dysregulation of the balance between Th9 cells and Treg cells might trigger aberrant immune responses, resulting in development and exacerbation of asthma and cancer. In this review, the development, differentiation, and function of Th9 cells and Treg cells, which are synergistically regulated by various factors including cytokine signals, transcriptional factors (TFs), costimulatory signals, microenvironment cues, metabolic pathways, and different signal pathways, will be discussed. In addition, we focus on the recent progress that has helped to achieve a better understanding of the roles of Th9 cells and Treg cells in allergic airway inflammation and tumor immunity. We also discuss how various factors moderate their responses in asthma and cancer. Finally, we summarize the recent findings regarding potential mechanisms for regulating the balance between Th9 and Treg cells in asthma and cancer. These advances provide opportunities for novel therapeutic strategies that are aimed at reestablishing the balance of these cells in the diseases.
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