哮喘性炎症和屋尘螨（HDM）暴露对肺驻留间充质干细胞（lrMSCs）丰度、免疫调节潜力和分化能力的影响
2025/08/31
摘要：
背景：组织驻留间充质干细胞，也称为间充质基质细胞（MSCs），在维持组织稳态和修复中起着关键作用。然而，它们在慢性炎症性疾病（如哮喘）中的功能仍不清楚。
目的：本研究旨在评估屋尘螨（HDM）诱导的哮喘性炎症对肺驻留（lr）MSCs的数量和功能的影响。
方法：通过鼻内给予HDM在雌性C57BL6/cmdb小鼠中诱导实验性哮喘。分离、扩增lrMSCs并通过流式细胞术和分化实验进行表征。分离人脂肪组织来源的（hAD）MSCs，并用HDM、LPS（脂多糖）或细胞因子进行刺激。与外周血单个核细胞（PBMCs）的共培养实验用于评估其免疫调节潜力。分析了基因表达、细胞因子水平和T细胞增殖情况。
结果：本研究显示，哮喘性肺部炎症显著减少了lrMSCs的数量。更重要的是，存留的lrMSCs表现出受损的分化潜能，并缺乏免疫调节功能。此外，我们发现将hAD-MSCs暴露于HDM和LPS同样导致其分化潜能受到明显抑制，并抑制了其免疫抑制活性。值得注意的是，即使存在PBMCs响应LPS和HDM而释放的促炎细胞因子，这种抑制作用仍然持续存在。此外，我们还发现，即使没有LPS和HDM的直接暴露，单独的炎症信号传导也能显著减少生长因子诱导的脂肪形成和骨形成。
结论：综上所述，我们的研究结果表明，哮喘性炎症不仅减少了lrMSCs的数量，还损害了它们的功能。这种损害可能通过限制lrMSCs的免疫调节作用，从而促进疾病的发展态势。
The influence of asthmatic inflammation and house dust mite (HDM) exposure on abundance, immune-modulatory potential, and differentiation capacity of the lung-resident mesenchymal stem cells (lrMSCs)
A.Walewska, M. Tynecka, S. Ksiezak, A. Tarasik, A. Janucik, K. Bondarczuk, et al.
Abstract
BACKGROUND:Tissue-resident mesenchymal stem cells, also known as mesenchymal stromal cells (MSCs), play a crucial role in maintaining tissue homeostasis and repair. However, their function in chronic inflammatory diseases, such as asthma, remains elusive.
OBJECTIVE:Here, we aimed to assess the influence of house dust mite (HDM)-induced asthmatic inflammation on the numbers and function of lung resident (lr)MSCs.
METHODS:Experimental asthma was induced in female C57BL6/cmdb mice via intranasal HDM administration. LrMSCs were isolated, expanded, and characterized by flow cytometry and differentiation assays. Human adipose tissue-derived (hAD)MSCs were isolated and stimulated with HDM, LPS, or cytokines. Co-culture experiments with peripheral blood mononuclear cells (PBMCs) assessed immunomodulatory potential. Gene expression, cytokine levels, and T-cell proliferation were analyzed.
RESULTS: Here, we showed that asthmatic lung inflammation significantly reduces the number of lrMSCs. More importantly, remaining lrMSCs showed impaired differentiation potential and lacked immunomodulatory functions. Furthermore, we found that exposure of hAD-MSCs to HDM and LPS similarly led to marked inhibition of differentiation potential and suppression of immunosuppressive activities. Notably, this inhibitory effect persisted despite the presence of pro-inflammatory cytokines released by PBMCs in response to LPS and HDM. Furthermore, we showed that inflammatory signaling alone, in the absence of direct LPS and HDM exposure, significantly reduces growth factor-induced adipogenesis and osteogenesis.
CONCLUSION:Taken together, our findings indicate that asthmatic inflammation not only reduces the number of lrMSCs but also impairs their function, potentially exacerbating disease progression by limiting their immunoregulatory role.
背景：组织驻留间充质干细胞，也称为间充质基质细胞（MSCs），在维持组织稳态和修复中起着关键作用。然而，它们在慢性炎症性疾病（如哮喘）中的功能仍不清楚。
目的：本研究旨在评估屋尘螨（HDM）诱导的哮喘性炎症对肺驻留（lr）MSCs的数量和功能的影响。
方法：通过鼻内给予HDM在雌性C57BL6/cmdb小鼠中诱导实验性哮喘。分离、扩增lrMSCs并通过流式细胞术和分化实验进行表征。分离人脂肪组织来源的（hAD）MSCs，并用HDM、LPS（脂多糖）或细胞因子进行刺激。与外周血单个核细胞（PBMCs）的共培养实验用于评估其免疫调节潜力。分析了基因表达、细胞因子水平和T细胞增殖情况。
结果：本研究显示，哮喘性肺部炎症显著减少了lrMSCs的数量。更重要的是，存留的lrMSCs表现出受损的分化潜能，并缺乏免疫调节功能。此外，我们发现将hAD-MSCs暴露于HDM和LPS同样导致其分化潜能受到明显抑制，并抑制了其免疫抑制活性。值得注意的是，即使存在PBMCs响应LPS和HDM而释放的促炎细胞因子，这种抑制作用仍然持续存在。此外，我们还发现，即使没有LPS和HDM的直接暴露，单独的炎症信号传导也能显著减少生长因子诱导的脂肪形成和骨形成。
结论：综上所述，我们的研究结果表明，哮喘性炎症不仅减少了lrMSCs的数量，还损害了它们的功能。这种损害可能通过限制lrMSCs的免疫调节作用，从而促进疾病的发展态势。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（Stem Cell Research & Therapy 2025 Vol. 16 Issue 1 DOI: ARTN 39610.1186/s13287-025-04520-1）
The influence of asthmatic inflammation and house dust mite (HDM) exposure on abundance, immune-modulatory potential, and differentiation capacity of the lung-resident mesenchymal stem cells (lrMSCs)
A.Walewska, M. Tynecka, S. Ksiezak, A. Tarasik, A. Janucik, K. Bondarczuk, et al.
Abstract
BACKGROUND:Tissue-resident mesenchymal stem cells, also known as mesenchymal stromal cells (MSCs), play a crucial role in maintaining tissue homeostasis and repair. However, their function in chronic inflammatory diseases, such as asthma, remains elusive.
OBJECTIVE:Here, we aimed to assess the influence of house dust mite (HDM)-induced asthmatic inflammation on the numbers and function of lung resident (lr)MSCs.
METHODS:Experimental asthma was induced in female C57BL6/cmdb mice via intranasal HDM administration. LrMSCs were isolated, expanded, and characterized by flow cytometry and differentiation assays. Human adipose tissue-derived (hAD)MSCs were isolated and stimulated with HDM, LPS, or cytokines. Co-culture experiments with peripheral blood mononuclear cells (PBMCs) assessed immunomodulatory potential. Gene expression, cytokine levels, and T-cell proliferation were analyzed.
RESULTS: Here, we showed that asthmatic lung inflammation significantly reduces the number of lrMSCs. More importantly, remaining lrMSCs showed impaired differentiation potential and lacked immunomodulatory functions. Furthermore, we found that exposure of hAD-MSCs to HDM and LPS similarly led to marked inhibition of differentiation potential and suppression of immunosuppressive activities. Notably, this inhibitory effect persisted despite the presence of pro-inflammatory cytokines released by PBMCs in response to LPS and HDM. Furthermore, we showed that inflammatory signaling alone, in the absence of direct LPS and HDM exposure, significantly reduces growth factor-induced adipogenesis and osteogenesis.
CONCLUSION:Taken together, our findings indicate that asthmatic inflammation not only reduces the number of lrMSCs but also impairs their function, potentially exacerbating disease progression by limiting their immunoregulatory role.
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小鼠呼吸道病毒感染后的上皮记忆导致抗原呈递的延长增强
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探索童年期虐待与哮喘的因果关联：一项孟德尔随机化研究
