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。

 
(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.)


 
 
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.
 
 


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