Although several studies have demonstrated that mesenchymal stem cells derived from adipose tissue (ASCs) can ameliorate allergic airway inflammation, the immunomodulatory mechanism of ASCs remains unclear. In this study, we investigated whether regulatory T cells (Tregs) induction is a potential mechanism in immunomodulatory effects of ASCs on allergic airway disease and how these induced Tregs orchestrate allergic inflammation. Intravenous administration of ASCs significantly reduced allergic symptoms and inhibited eosinophilic inflammation. Airway hyperresponsiveness, total immune cell and eosinophils in the bronchoalveolar lavage fluid, mucus production, and serum allergen-specific IgE and IgG1 were significantly reduced after ASCs administration. ASCs significantly inhibited Th2 cytokines (IL-4, IL-5, and IL-13) and enhanced Th1 cytokine (IFN-γ) and regulatory cytokines (IL-10 and TGF-β) in the bronchoalveolar lavage fluid and lung draining lymph nodes. Furthermore, levels of IDO, TGF-β, and PGE₂were significantly increased after ASCs administration. Interestingly, this upregulation was accompanied by increased Treg populations. In conclusion, ASCs ameliorated allergic airway inflammation and improved lung function through the induction of Treg expansion. The induction of Treg by ASCs involves the secretion of soluble factors such as IDO, TGF-β, and PGE₂and Treg might be involved in the downregulation of Th2 cytokines and upregulation of Th1 cytokines production.

Kim SD, et al. World J Mens Health. 2018 Jan;36:e19. https://doi.org/10.5534/wjmh.180017

Although stem cell-derived extracellular vesicles (EVs) have been shown to facilitate regeneration of injured tissue, there is no report that evaluates the immune-modulating effect of stem cell-derived EVs on Th2-mediated inflammation. In this study, we evaluated the immunomodulatory effects of adipose stem cells (ASCs)-derived EVs on Th2-mediated inflammation induced by Aspergillus protease antigen in lung epithelial cells. The EVs were isolated from supernatant of ASCs and the diameters of EVs were measured by using dynamic light scattering. The mice primary lung epithelial cells and mouse lung epithelial cell line (MLE12) were pre-treated with 200 ng/ml of Aspergillus protease and then treated with 1 μg/ml of ASC-derived EVs. Real time PCR was performed to determine the expression levels of eotaxin, IL-25, TGF-β, and IL-10 mRNAs after EV treatment. To evaluate the role of EVs in macrophage polarization and dendritic cells (DCs) differentiation, in vitro bone marrow-derived macrophage and DCs stimulation assay was performed. EV treatment significantly decreased the expression of eotaxin and IL-25 and increased TGF-β and IL-10 in both lung epithelial cells. EV treatment significantly increased the expression of co-stimulatory molecules such as CD40, CD80, and CD 86 in immature DCs. Furthermore, EV treatment significantly enhanced the gene expression of M2 macrophage marker such as Arg1, CCL22, IL-10, and TGF-β. In conclusion, EVs of ASCs ameliorated Th2-mediated inflammation induced by Aspergillus protease antigen through the activation of dendritic cells and M2 macrophage, accompanied by down-regulation of eotaxin and IL-25, and up-regulation of TGF-β and IL-10 in mouse lung epithelial cells.

To examine correlations among rating scales and findings suggestive of tracheal aspiration and pharyngeal residue between fiberoptic endoscopic evaluation of swallowing (FEES) and videofluoroscopic swallowing study (VFSS) in dysphagia patients. We studied patients referred to our hospital for dysphagia assessment. Three raters judged the residue severity and laryngeal penetration or tracheal aspiration of FEES and VFSS. The raters applied the Penetration-Aspiration Scale (PAS) for tracheal aspiration and pixel-based circumscribed area ratio and Yale Pharyngeal Residue Severity for post-swallow residue in VFSS and FEES, respectively. Anatomy-physiologic findings during FEES associated with tracheal aspiration were also analyzed. A total of 178 participants were enrolled in our study. In correlation analysis, PAS (r=0.74), vallecula retention (r=0.76), and pyriform sinus retention (r=0.78) showed strong positive correlations between FEES and VFSS. Intra-rater agreement between VFSS and FEES was good for PAS (κ=0.65) and vallecula (κ=0.65) and pyriform sinus retention (κ=0.69). Among 72 patients who showed subglottic shelf residue, a suspected finding of aspiration, in FEES, 68 had concomitant tracheal aspiration during VFSS. Both vocal fold hypomobility and glottic gap during phonation were significantly associated with findings suggestive of tracheal aspiration during FEES (p<0.05). Quantitative and reliable aspiration and post swallow residue rating scales showed strong positive correlations and good agreement between VFSS and FEES.