Abstract
Asthma is a chronic eosinophilic airway disease characterized by type 2 helper T cell-driven inflammation. Adipose stem cells (ASCs) and the ASC culture supernatant are known to improve allergic airway inflammation; however, the immunomodulatory effects of ASC-derived extracellular vesicles (EVs) on allergic airway diseases remain unclear. Thus, we assessed the effects of ASC-derived EVs on allergic airway inflammation in a mouse model of asthma. EVs were isolated from the culture supernatant of murine ASCs and characterized. Six-week-old female C57BL/6 mice were sensitized to ovalbumin (OVA) by intraperitoneal injection and challenged intranasally with OVA. Before the OVA challenge, 10 μg/50 μl of ASC-derived EVs was administered intranasally to the experimental group. ASC-derived EVs significantly attenuated airway hyperresponsiveness (AHR) in asthmatic mice (p = 0.023). ASC-derived EVs resulted in a remarkable reduction of the total number of inflammatory cells (p = 0.005) and eosinophils (p = 0.023) in the bronchoalveolar lavage fluid (BALF), the degree of eosinophilic lung inflammation (p < 0.001), and the serum total and OVA-specific immunoglobulin (Ig)E (p = 0.048 and p = 0.001) and total IgG1 (p < 0.001). Interleukin- (IL-) 4 was significantly inhibited with ASC-derived EV pretreatment in the BALF and lung draining lymph nodes (LLNs) (p = 0.040 and p = 0.011). Furthermore, ASC-derived EV administration resulted in a significant increase of the regulatory T cell (Treg) populations in LLNs. ASC-derived EVs alleviated AHR and allergic airway inflammation caused by the induction of Treg expansion in a mouse model of asthma. There seems to be a role for ASC-derived EVs as a modifier in allergic airway disease.
Highlights
Asthma is a chronic eosinophilic airway disease mainly driven by excessive activation of type 2 helper T (Th2) cells [1]
Previous studies have shown that Mesenchymal stem cells (MSCs), including those derived from adipose tissuederived stem cells (ASCs), can alleviate allergic airway inflammation in asthmatic mice [7,8,9]
transmission electron microscope (TEM) showed that ASC-derived extracellular vesicles (EVs) were composed of lipid bilayers and were spherical in shape (Figure 2(a))
Summary
Asthma is a chronic eosinophilic airway disease mainly driven by excessive activation of type 2 helper T (Th2) cells [1]. Th2 cell-driven inflammation is reflected by a significant increase in interleukin- (IL-) 4, IL-5, and IL-13 levels, causing airway eosinophilic inflammation, high serum immunoglobulin E (IgE) levels, and airway hyperresponsiveness (AHR) [2]. Mesenchymal stem cells (MSCs) can regulate inflammation and immune responses [6]. Previous studies have shown that MSCs, including those derived from adipose tissuederived stem cells (ASCs), can alleviate allergic airway inflammation in asthmatic mice [7,8,9]. ASC administration before the allergen challenge inhibited AHR, lung inflammation, and Th2 cytokine production through inhibition of Th2 cell activity in an asthmatic murine model [7].
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