Pulmonary allergic responses augment interleukin-13 secretion by circulating basophils yet suppress interferon-alpha from plasmacytoid dendritic cells.
Pulmonary allergic responses augment interleukin-13 secretion by circulating basophils yet suppress interferon-alpha from plasmacytoid dendritic cells.
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DOI：
10.1111/j.1365-2222.2010.03456.x
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发表时间：
2010-05
期刊：
影响因子：
--
通讯作者：
Liu MC
中科院分区：
文献类型：
--
作者：
Schroeder JT;Bieneman AP;Chichester KL;Breslin L;Xiao H;Liu MC
过敏性炎症过程可能具有通过循环白细胞的作用进行全身传播的能力。因此，来自过敏个体的嗜碱性粒细胞通常会被“启动”，正如它们在体外的高反应性所证明的那样。 IFN-α 主要由浆细胞样 DC 分泌，在体外抑制嗜碱性粒细胞引发 IL-13。这项研究寻求实验性过敏原挑战过程中产生的体内相关性，支持嗜碱性粒细胞和 pDC 之间的“轴相互作用”。通过对肺部进行分段过敏原激发，研究了志愿者 (n=10) 在接触过敏原之前和之后 24 小时对血液中两种细胞类型的免疫反应。然后将这些反应与支气管肺泡灌洗液中测量的炎症参数相关联。在血液中，分段过敏原攻击显着增加了 IL-3 诱导的嗜碱性粒细胞的 IL-13 分泌 (p=0.009)，但减少了 CpG 刺激的浆细胞样树突状细胞分泌的 IFN-α (p=0.018)。两个参数呈负相关（p=0.0015），至少在分泌后者的受试者中是这样。循环嗜碱性粒细胞 IL-13 反应进一步与节段性过敏原激发后支气管肺泡灌洗参数相关，包括 IL-13 蛋白 (p=0.04)、嗜碱性粒细胞 (p=0.051)、嗜酸性粒细胞 (p=0.0018) 和总细胞计数 (p<0.003)。支气管肺泡灌洗液中的嗜碱性粒细胞和 IL-13 水平同样相关 (p=0.0002)。这些结果支持了一种免疫调节机制，即过敏原减少先天免疫反应和浆细胞样树突状细胞产生的干扰素-α，从而导致过敏原暴露部位的炎症和嗜碱性粒细胞细胞因子的产生增强。
Allergic inflammatory processes may have the capacity to propagate systemically through the actions of circulating leukocytes. Consequently, basophils from allergic individuals are often “primed”, as evidenced by their hyper-responsiveness in vitro. IFN-α, secreted predominately by plasmacytoid DCs, suppresses basophil priming for IL-13 production in vitro. This study sought in vivo correlates, arising during experimental allergen challenge, that support an “axis-interplay” between basophils and pDCs. Using segmental allergen challenge in the lung, the immune responses of both cell types from blood were investigated in volunteers (n=10) before and 24h after allergen exposure. These responses were then correlated with inflammatory parameters measured in bronchoalveolar lavage fluids. In blood, segmental allergen challenge significantly augmented IL-13 secretion by basophils induced by IL-3 (p=0.009) yet reduced IFN-α secreted by plasmacytoid dendritic cells stimulated with CpG (p=0.018). Both parameters were negatively correlated (p=0.0015), at least among those subjects secreting the latter. Circulating basophil IL-13 responses further correlated with post-segmental allergen challenge bronchoalveolar lavage parameters including IL-13 protein (p=0.04), basophil (p=0.051), eosinophil (p=0.0018) and total cell counts (p<0.003). Basophil and IL-13 levels in bronchoalveolar lavage likewise correlated (p=0.0002). These results support a mechanism of immune regulation whereby allergen reduces innate immune responses and IFN-α production by plasmacytoid dendritic cells, resulting in enhanced inflammation and basophil cytokine production at sites of allergen exposure.
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影响因子：
4.4
作者：
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