Cho Kyu-Sup, Park Mi-Kyung, Kang Shin-Ae, Park Hee-Young, Hong Sung-Lyong, Park Hye-Kyung, Yu Hak-Sun, Roh Hwan-Jung
Department of Otorhinolaryngology and Biomedical Research Institute, Pusan National University Hospital, Busan 602-739, Republic of Korea.
Department of Parasitology, Pusan National University School of Medicine, Yangsan 626-870, Republic of Korea.
Mediators Inflamm. 2014;2014:436476. doi: 10.1155/2014/436476. Epub 2014 Aug 26.
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 PGE2 were 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 PGE2 and Treg might be involved in the downregulation of Th2 cytokines and upregulation of Th1 cytokines production.
尽管多项研究表明,脂肪组织来源的间充质干细胞(ASCs)可改善过敏性气道炎症,但ASCs的免疫调节机制仍不清楚。在本研究中,我们调查了调节性T细胞(Tregs)的诱导是否是ASCs对过敏性气道疾病免疫调节作用的潜在机制,以及这些诱导的Tregs如何协调过敏性炎症。静脉注射ASCs可显著减轻过敏症状并抑制嗜酸性粒细胞炎症。注射ASCs后,气道高反应性、支气管肺泡灌洗液中的总免疫细胞和嗜酸性粒细胞、黏液分泌以及血清过敏原特异性IgE和IgG1均显著降低。ASCs显著抑制支气管肺泡灌洗液和肺引流淋巴结中的Th2细胞因子(IL-4、IL-5和IL-13),并增强Th1细胞因子(IFN-γ)和调节性细胞因子(IL-10和TGF-β)。此外,注射ASCs后,IDO、TGF-β和PGE2的水平显著升高。有趣的是,这种上调伴随着Treg群体的增加。总之,ASCs通过诱导Treg扩增改善了过敏性气道炎症并改善了肺功能。ASCs对Treg的诱导涉及可溶性因子如IDO、TGF-β和PGE2的分泌,并且Treg可能参与Th2细胞因子的下调和Th1细胞因子产生的上调。