Abstract
The incidence of asthma has increased in recent decades. Although corticosteroids and bronchodilators are used in clinical practice, the control of asthma remains a challenge. Allergic asthma is characterized airway inflammation mediated by type 2 immune response. Group 2 innate lymphoid cells (ILC2s) are an important source of type 2 cytokines IL-5 and IL-13, which contribute to the progress of asthma. Jia-Wei-Yu-Ping-Feng-San (JWYPFS), a traditional Chinese medicine, has been widely used to treat asthma in China. In this study we investigated the mechanisms of JWYPFS in the treatment of asthma, especially the effect on ILC2s important in airway inflammation. Female C57BL/6 mice were sensitized and challenged with OVA to establish a model of allergic asthma. Airway hyperresponsiveness was examined by direct airway resistance analysis. Inflammatory cell counts were determined in bronchoalveolar lavage fluid (BALF). Inflammatory cell infiltration and mucus hypersecretion in lung tissue sections was observed by HE and PAS staining, respectively. The numbers and proportions of ILC2s as well as the ILC2s-related transcription factors GATA3, IRF4, and type 2 cytokines were measured in lung tissue samples. Additionally, ILC2s were collected from mouse lung; ILC2s-related cytokines and GATA3 and IRF4 were evaluated after IL-33-induced activation of ILC2s in vitro. Elevated inflammatory cells, mucus secretion, airway hyperresponsiveness and type 2 cytokines in the OVA-treated asthma group indicated that an allergic asthma model had been established. JWYPFS treatment attenuated airway resistance and reduced inflammatory cells including eosinophils, and inhibited mucus production and type 2 cytokines in these asthmatic mice. Moreover, JWYPFS treatment dramatically decreased the numbers and proportions of ILC2s and the mRNA levels of GATA3 and IRF4. In an in vitro experiment JWYPFS significantly suppressed GATA3, IRF4 and type 2 cytokine expression, including IL-5 and IL-13 in IL-33-stimulated ILC2s. JWYPFS alleviates ILC2s-mediated airway inflammation, suggesting that JWYPFS might be an effective agent to treat allergic asthma.
Highlights
Asthma is a common chronic inflammatory disease of the airways
The major constituents in JWYPFS granules were analyzed by High performance liquid chromatography (HPLC)-Q-TOF-MS (Figure 1). 21 compounds are selected for LC-MS analysis, owing to these compounds are major bioactive constituents and the markers for quality control of these herbs, which are recommended by the Chinese Pharmacopeia 2020
The results show that the expression of IL-5 and IL-13 in the OVA group mice was significantly increased when compared to the control group, and these increases were reversed after the treatment with JWYPFS or DEX (Figure 5)
Summary
Asthma is a common chronic inflammatory disease of the airways. It affects approximately 1–18% of the population in different countries, and about 350 million people suffer from asthma worldwide (Ish et al, 2020). Asthma causes a heavy burden to governments, families and patients (Loftus and Wise, 2015). Many previous studies have indicated that T helper 2 (Th2) cells play a crucial role in the progression of the asthma disease process (Wills-Karp et al, 1998; Kips et al, 2001; Choy et al, 2015). The discovery of innate lymphoid cells (ILCs) has changed our understanding of the pathogenesis of asthma over the last decade
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