调节性树突状细胞抑制哮喘过敏原特异性IgG1抗体反应的直接和间接证据比较
2018/01/15
摘要
IL-10分化树突状细胞（DC10）在小鼠中可以逆转哮喘表型，但其抑制哮喘B细胞应答机制尚不明确。本研究就哮喘中DC10和DC10诱导Treg从而影响IgG1生成进行机制研究。研究发现在气道激发试验之后肺内OVA特异性IgG1分泌B细胞数目出现快速下降，而腹膜内DC10治疗则无法予以扩增（p>0.05）。然而，在超过2周的时间里，骨髓（5+/-7.2%; p≤0.01）和脾脏(65+/-17.8%; p≤0.05)中IgG1-B细胞数目下降增加。哮喘小鼠气道直接给予OVA作用过的DC10，2天后评估发现肺内IgG1-B细胞应答率下降33+/-9.7% (p≤0.01)，而与哮喘飞细胞悬液共培养组IgG1分泌B细胞数量下降56.5+/-9.7% (p≤0.01)。而这一效应有赖于DC10细胞表面携带完整抗原。DC10完成细胞吞噬或完全处理过抗原则无法抑制B细胞应答，尽管其可以一直哮喘Th2细胞应答。本研究提示给予DC10诱导Treg可以有效抑制哮喘T和B细胞（IgE和IgG1）应答；在体外实验中，经DC10处理OVA哮喘小鼠肺内CD4+细胞或Treg可以抑制B细胞和IgG1生成分别达到52.2+/-8.7% (p≤0.001) or 44.6+/-12.2% (p≤0.05)。而直接气道给予DC10诱导Treg则并无类型效应(p≤0.05)。总而言之，DC10治疗可以下调哮喘小鼠OVA特异性B细胞应答。而细胞表面携带完整抗原DC10则会有损于这一应答，DC10诱导Treg对于这一过程的完全实现至关重要。这也说明在哮喘小鼠中，感染性耐受力对于调节性DC对于B细胞应答的调控发挥重要作用。
Contributions of direct versus indirect mechanisms for regulatory dendritic cell suppression of asthmatic allergen-specific IgG1 antibody responses.
PLoS One. 2018 Jan 2;13(1):e0190414. doi: 10.1371/journal.pone.0190414. eCollection 2018.
Ma Y, Dawicki W, Zhang X, Gordon JR.
Abstract
IL-10-differentiated dendritic cells (DC10) can reverse the asthma phenotype in mice, but how they suppress the asthmatic B cell response is unclear. Herein we assessed the mechanism(s) by which DC10 and DC10-induced Treg affect IgG1 production in asthma. We observed a rapid decline in lung-resident OVA-specific IgG1-secreting B cells on cessation of airway allergen challenge, and intraperitoneal DC10 therapy did not amplify that (p>0.05). It did however increase the loss of IgG1-B cells from the bone marrow (by 45+/-7.2%; p≤0.01) and spleen (by 65+/-17.8%; p≤0.05) over 2 wk. Delivery of OVA-loaded DC10 directly into the airways of asthmatic mice decreased the lung IgG1 B cell response assessed 2 dy later by 33+/-9.7% (p≤0.01), while their co-culture with asthmatic lung cell suspensions reduced the numbers of IgG1-secreting cells by 56.5+/-9.7% (p≤0.01). This effect was dependent on the DC10 carrying intact allergen on their cell surface; DC10 that had phagocytosed and fully processed their allergen were unable to suppress B cell responses, although they did suppress asthmatic Th2 cell responses. We had shown that therapeutic delivery of DC10-induced Treg can effectively suppress asthmatic T and B cell (IgE and IgG1) responses; herein CD4+ cells or Treg from the lungs of DC10-treated OVA-asthmatic mice suppressed in vitro B cell IgG1 production by 52.2+/-8.7% (p≤0.001) or 44.6+/-12.2% (p≤0.05), respectively, but delivery of DC10-induced Treg directly into the airways of asthmatic mice had no discernible impact over 2 dy on the numbers of lung IgG1-secreting cells (p≥0.05). In summary, DC10 treatment down-regulates OVA-specific B cell responses of asthmatic mice. While DC10 that carry intact allergen on their cell surface can dampen this response, DC10-induced Treg are critical for full realization of this outcome. This suggests that infectious tolerance is an essential element in regulatory DC control of the B cell response in allergic asthma.
IL-10分化树突状细胞（DC10）在小鼠中可以逆转哮喘表型，但其抑制哮喘B细胞应答机制尚不明确。本研究就哮喘中DC10和DC10诱导Treg从而影响IgG1生成进行机制研究。研究发现在气道激发试验之后肺内OVA特异性IgG1分泌B细胞数目出现快速下降，而腹膜内DC10治疗则无法予以扩增（p>0.05）。然而，在超过2周的时间里，骨髓（5+/-7.2%; p≤0.01）和脾脏(65+/-17.8%; p≤0.05)中IgG1-B细胞数目下降增加。哮喘小鼠气道直接给予OVA作用过的DC10，2天后评估发现肺内IgG1-B细胞应答率下降33+/-9.7% (p≤0.01)，而与哮喘飞细胞悬液共培养组IgG1分泌B细胞数量下降56.5+/-9.7% (p≤0.01)。而这一效应有赖于DC10细胞表面携带完整抗原。DC10完成细胞吞噬或完全处理过抗原则无法抑制B细胞应答，尽管其可以一直哮喘Th2细胞应答。本研究提示给予DC10诱导Treg可以有效抑制哮喘T和B细胞（IgE和IgG1）应答；在体外实验中，经DC10处理OVA哮喘小鼠肺内CD4+细胞或Treg可以抑制B细胞和IgG1生成分别达到52.2+/-8.7% (p≤0.001) or 44.6+/-12.2% (p≤0.05)。而直接气道给予DC10诱导Treg则并无类型效应(p≤0.05)。总而言之，DC10治疗可以下调哮喘小鼠OVA特异性B细胞应答。而细胞表面携带完整抗原DC10则会有损于这一应答，DC10诱导Treg对于这一过程的完全实现至关重要。这也说明在哮喘小鼠中，感染性耐受力对于调节性DC对于B细胞应答的调控发挥重要作用。
（上海交通大学医学院附属瑞金医院呼吸与危重症医学科 周剑平 万欢英 摘译）
（PLoS One. 2018 Jan 2;13(1):e0190414. doi: 10.1371/journal.pone.0190414. eCollection 2018.）
（PLoS One. 2018 Jan 2;13(1):e0190414. doi: 10.1371/journal.pone.0190414. eCollection 2018.）
Contributions of direct versus indirect mechanisms for regulatory dendritic cell suppression of asthmatic allergen-specific IgG1 antibody responses.
PLoS One. 2018 Jan 2;13(1):e0190414. doi: 10.1371/journal.pone.0190414. eCollection 2018.
Ma Y, Dawicki W, Zhang X, Gordon JR.
Abstract
IL-10-differentiated dendritic cells (DC10) can reverse the asthma phenotype in mice, but how they suppress the asthmatic B cell response is unclear. Herein we assessed the mechanism(s) by which DC10 and DC10-induced Treg affect IgG1 production in asthma. We observed a rapid decline in lung-resident OVA-specific IgG1-secreting B cells on cessation of airway allergen challenge, and intraperitoneal DC10 therapy did not amplify that (p>0.05). It did however increase the loss of IgG1-B cells from the bone marrow (by 45+/-7.2%; p≤0.01) and spleen (by 65+/-17.8%; p≤0.05) over 2 wk. Delivery of OVA-loaded DC10 directly into the airways of asthmatic mice decreased the lung IgG1 B cell response assessed 2 dy later by 33+/-9.7% (p≤0.01), while their co-culture with asthmatic lung cell suspensions reduced the numbers of IgG1-secreting cells by 56.5+/-9.7% (p≤0.01). This effect was dependent on the DC10 carrying intact allergen on their cell surface; DC10 that had phagocytosed and fully processed their allergen were unable to suppress B cell responses, although they did suppress asthmatic Th2 cell responses. We had shown that therapeutic delivery of DC10-induced Treg can effectively suppress asthmatic T and B cell (IgE and IgG1) responses; herein CD4+ cells or Treg from the lungs of DC10-treated OVA-asthmatic mice suppressed in vitro B cell IgG1 production by 52.2+/-8.7% (p≤0.001) or 44.6+/-12.2% (p≤0.05), respectively, but delivery of DC10-induced Treg directly into the airways of asthmatic mice had no discernible impact over 2 dy on the numbers of lung IgG1-secreting cells (p≥0.05). In summary, DC10 treatment down-regulates OVA-specific B cell responses of asthmatic mice. While DC10 that carry intact allergen on their cell surface can dampen this response, DC10-induced Treg are critical for full realization of this outcome. This suggests that infectious tolerance is an essential element in regulatory DC control of the B cell response in allergic asthma.
上一篇：
重症哮喘的病理生理机制：这仅仅是开始
下一篇：
早期吸入性过敏原暴露可增强经树突状细胞介导的抗病毒免疫功能和T细胞启动
