hMSCs suppress neutrophil-dominant airway inflammation in a murine model of asthma.
hMSCs suppress neutrophil-dominant airway inflammation in a murine model of asthma.
复制标题
DOI：
10.1038/emm.2016.135
复制
发表时间：
2017-01-27
影响因子：
12.8
通讯作者：
Cho YS
中科院分区：
文献类型：
--
作者：
Hong GH;Kwon HS;Lee KY;Ha EH;Moon KA;Kim SW;Oh W;Kim TB;Moon HB;Cho YS
虽然慢性嗜酸性粒细胞炎症是哮喘患者的共同特征，但一些患者有中性粒细胞为主的炎症，已知这与严重哮喘有关。人间充质干细胞（hMSCs）在治疗多种难治性免疫疾病方面显示出良好的前景。因此，对于目前治疗无效的嗜中性粒细胞为主炎症的哮喘患者，hMSCs可能是另一种治疗选择。BALB/c小鼠暴露于卵清蛋白和多肌苷：多胞酸（Poly I: c）诱导的中性粒细胞气道炎症，并用hMSCs进行全身处理，观察hMSCs是否能调节中性粒细胞气道炎症。此外，研究人员还评估了hMSC与来自哮喘患者的抗cd3 / cd28刺激的外周血单个核细胞（PBMCs）或人支气管上皮细胞系BEAS-2B细胞共培养时细胞因子的产生，以评估对hMSC治疗的反应。支气管肺泡灌洗液（BALF）中免疫细胞总数明显减少，特别是中性粒细胞浸润明显减弱。这种现象伴随着BALF中CXCL15产量的减少。与hMSCs共培养的BEAS-2B细胞IL-8分泌减少。此外，与hMSCs一起培养的人PBMCs中IL-4、IL-13和IFN-γ的分泌减少，而IL-10的分泌则大大增加。我们的数据表明，hMSCs可能通过下调中性粒细胞趋化因子的产生和调节t细胞反应来减少中性粒细胞气道炎症。
Although chronic eosinophilic inflammation is a common feature in patients with asthma, some patients have neutrophil-dominant inflammation, which is known to be associated with severe asthma.Human mesenchymal stem cells (hMSCs) have shown promise in treating various refractory immunological diseases. Thus, hMSCs may represent an alternative therapeutic option for asthma patients with neutrophil-dominant inflammation, in whom current treatments are ineffective. BALB/c mice exposed to ovalbumin and polyinosinic:polycytidylic acid (Poly I:C) to induce neutrophilic airway inflammation were systemically treated with hMSCs to examine whether the hMSCs can modulate neutrophilic airway inflammation. In addition, cytokine production was evaluated in co-cultures of hMSCs with either anti-CD3/CD28-stimulated peripheral blood mononuclear cells (PBMCs) obtained from asthmatic patients or cells of the human bronchial epithelial cell line BEAS-2B to assess the response to hMSC treatment. The total number of immune cells in bronchoalveolar lavage fluid (BALF) showed a dramatic decrease in hMSC-treated asthmatic mice, and, in particular, neutrophilic infiltration was significantly attenuated. This phenomenon was accompanied by reduced CXCL15 production in the BALF. BEAS-2B cells co-cultured with hMSCs showed reduced secretion of IL-8. Moreover, decreased secretion of IL-4, IL-13 and IFN-γ was observed when human PBMCs were cultured with hMSCs, whereas IL-10 production was greatly enhanced. Our data imply that hMSCs may have a role in reducing neutrophilic airway inflammation by downregulating neutrophil chemokine production and modulating T-cell responses.