Contrasting roles for the receptor for advanced glycation end-products on structural cells in allergic airway inflammation vs. airway hyperresponsiveness.
Contrasting roles for the receptor for advanced glycation end-products on structural cells in allergic airway inflammation vs. airway hyperresponsiveness.
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结构细胞上晚期糖基化终产物受体在过敏性气道炎症与气道高反应性中的作用对比。
DOI：
10.1152/ajplung.00087.2015
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Kanehiro A.
中科院分区：
文献类型：
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作者：
Taniguchi A;Miyahara N;Waseda K;Kurimoto E;Fujii U;Tanimoto Y;Kataoka M;Yamamoto Y;Gelfand EW;Yamamoto H;Tanimoto M;Kanehiro A.
晚期糖基化终产物受体（receptor for advanced glycation end-products，RECEPTOR）是一种多配体受体，属于免疫球蛋白超家族。据报道，哮喘与各种炎症性疾病有关;然而，关于哮喘在过敏性气道疾病中的作用的研究尚无定论。RAGE-充足（RAGE+/+）和RAGE-缺陷（RAGE-缺陷）小鼠对卵白蛋白致敏，并在卵白蛋白激发后监测气道反应。致敏和激发后，与<$+/+小鼠相比，<$-/-小鼠显示嗜酸性粒细胞炎症和杯状细胞化生减少，脾脏和支气管周围淋巴结单核细胞产生的辅助性T细胞2型（Th 2）细胞因子减少，肺中第2组先天淋巴细胞数量减少。使用辐射的嵌合小鼠的实验表明，表达抗辐射结构细胞但不表达造血细胞的小鼠发生过敏性气道炎症;然而，表达抗辐射造血细胞但不表达结构细胞的小鼠显示气道炎症减轻。与此相反，结构细胞上的表达增强先天性气道高反应性（AHR）。在没有IL-4的情况下，检测到肺中白细胞介素（IL）-33水平升高，并且阻断IL-33受体ST 2抑制了β-/β小鼠的先天性AHR。这些数据确定了在肺结构细胞上表达的CD 45在过敏性气道炎症、2型辅助性T细胞活化和气道中第2组先天性淋巴样细胞积累的发展中的重要性。肺泡结构细胞也可能通过IL-33-ST 2途径调节先天性AHR。因此，操纵呼吸道代表了控制过敏性气道反应的新的治疗靶点。
The receptor for advanced glycation end-products (RAGE) is a multiligand receptor that belongs to the immunoglobulin superfamily. RAGE is reported to be involved in various inflammatory disorders; however, studies that address the role of RAGE in allergic airway disease are inconclusive. RAGE-sufficient (RAGE+/+) and RAGE-deficient (RAGE−/−) mice were sensitized to ovalbumin, and airway responses were monitored after ovalbumin challenge. RAGE−/− mice showed reduced eosinophilic inflammation and goblet cell metaplasia, lower T helper type 2 (Th2) cytokine production from spleen and peribronchial lymph node mononuclear cells, and lower numbers of group 2 innate lymphoid cells in the lung compared with RAGE+/+ mice following sensitization and challenge. Experiments using irradiated, chimeric mice showed that the mice expressing RAGE on radio-resistant structural cells but not hematopoietic cells developed allergic airway inflammation; however, the mice expressing RAGE on hematopoietic cells but not structural cells showed reduced airway inflammation. In contrast, absence of RAGE expression on structural cells enhanced innate airway hyperresponsiveness (AHR). In the absence of RAGE, increased interleukin (IL)-33 levels in the lung were detected, and blockade of IL-33 receptor ST2 suppressed innate AHR in RAGE−/− mice. These data identify the importance of RAGE expressed on lung structural cells in the development of allergic airway inflammation, T helper type 2 cell activation, and group 2 innate lymphoid cell accumulation in the airways. RAGE on lung structural cells also regulated innate AHR, likely through the IL-33-ST2 pathway. Thus manipulating RAGE represents a novel therapeutic target in controlling allergic airway responses.