University of Chicago, Section of Pulmonary and Critical Care Medicine, Chicago, IL 60637, USA.
Respir Res. 2013 Jan 18;14(1):4. doi: 10.1186/1465-9921-14-4.
Human leukocyte antigen (HLA)-G is a nonclassical class I antigen with immunomodulatory roles including up-regulation of suppressor T regulatory lymphocytes. HLA-G was recently identified as an asthma susceptibility gene, and expression of a soluble isoform, HLA-G5, has been demonstrated in human airway epithelium. Increased presence of HLA-G5 has been demonstrated in bronchoalveolar lavage fluid recovered from patients with mild asthma; this suggests a role for this isoform in modulating airway inflammation though the mechanisms by which this occurs is unclear. Airway inflammation associated with Th2 cytokines such as IL-4 and IL-13 is a principal feature of asthma, but whether these cytokines elicit expression of HLA-G is not known.
We examined gene and protein expression of both soluble (G5) and membrane-bound (G1) HLA-G isoforms in primary differentiated human airway epithelial cells collected from normal lungs and grown in air-liquid interface culture. Cells were treated with up to 10 ng/ml of either IL-4, IL-5, or IL-13, or 100 ng/ml of the immunomodulatory cytokine IL-10, or 10,000 U/ml of the Th1-associated cytokine interferon-beta, for 24 hr, after which RNA was isolated for evaluation by quantitative PCR and protein was collected for Western blot analysis.
HLA-G5 but not G1 was present in dAEC as demonstrated by quantitative PCR, western blot and confocal microscopy. Neither G5 nor G1 expression was increased by the Th2-associated cytokines IL-4, IL-5 or IL-13 over 24 hr, nor after treatment with IL-10, but was increased 4.5 ± 1.4 fold after treatment with 10,000 U/ml interferon-beta.
These data demonstrate the constitutive expression of a T lymphocyte regulatory molecule in differentiated human airway epithelial cells that is not modulated by Th2-associated cytokines.
人类白细胞抗原（HLA）-G 是一种具有免疫调节作用的非经典 I 类抗原，包括上调抑制性 T 调节性淋巴细胞。HLA-G 最近被鉴定为哮喘易感性基因，并且已经在人呼吸道上皮中鉴定出可溶性同种型 HLA-G5 的表达。在患有轻度哮喘的患者的支气管肺泡灌洗液中已经证明 HLA-G5 的存在增加；这表明该同种型在调节气道炎症中起作用，尽管发生这种作用的机制尚不清楚。与 Th2 细胞因子（如 IL-4 和 IL-13）相关的气道炎症是哮喘的主要特征，但这些细胞因子是否会引起 HLA-G 的表达尚不清楚。
我们检查了从正常肺中收集并在气液界面培养中分化的人呼吸道上皮细胞中可溶性（G5）和膜结合（G1）HLA-G 同种型的基因和蛋白表达。将细胞用高达 10 ng/ml 的 IL-4、IL-5 或 IL-13 或 100 ng/ml 的免疫调节细胞因子 IL-10 或 10,000 U/ml 的 Th1 相关细胞因子干扰素-β处理 24 小时，然后分离 RNA 进行定量 PCR 评估，并收集蛋白质进行 Western blot 分析。
定量 PCR、Western blot 和共聚焦显微镜显示，dAEC 中存在 HLA-G5，但不存在 G1。在 24 小时内，Th2 相关细胞因子 IL-4、IL-5 或 IL-13 均未增加 G5 或 G1 的表达，用 IL-10 处理后也未增加，但用 10,000 U/ml 干扰素-β处理后增加了 4.5±1.4 倍。
这些数据表明，在分化的人呼吸道上皮细胞中表达一种 T 淋巴细胞调节分子，该分子不受 Th2 相关细胞因子的调节。
