CRTH2 expression on T cells in asthma.

CRTH2 expression on T cells in asthma.
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DOI:
10.1111/j.1365-2249.2010.04161.x
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发表时间:
2010-07-01
影响因子:
4.6
通讯作者:
Wardlaw AJ
Wardlaw AJ
中科院分区:
医学3区
文献类型:
--
作者:
Mutalithas K;Guillen C;Day C;Brightling CE;Pavord ID;Wardlaw AJ

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肥大细胞衍生的前列腺素D2(PGD2)是哮喘患者过敏原攻击后立即在呼吸道内发现的主要前列腺素。体外研究表明,PGD2对嗜酸性粒细胞和辅助性T细胞2型(Th2)有趋化作用。这是通过PGD2与Th2淋巴细胞上表达的G蛋白偶联趋化因子受体同源分子(CRTH2)相互作用而发生的。CRTH2的表达对Th2细胞具有高度的选择性。应用流式细胞术研究了哮喘患者和正常人外周血和支气管肺泡灌洗液中T细胞表面CRTH2的表达。CRTH2在哮喘患者(1·8%±0·2)和正常人(1·6%±0·2)的血T细胞中仅有少量表达。IL-4+/IL-13+T细胞较干扰素-γ+T细胞显著富含CRTH2(P&lt;0·001)。哮喘患者支气管肺泡灌洗液(BAL)中有少量CRTH2+T细胞(2.3%±0.6%),与正常人(0.3%±0.1%)比较差异有统计学意义(P<0.05)。哮喘组和正常人BAL中PGD2含量相近。在同一受试者的配对血-BAL样本中,与哮喘患者的血液相比,BAL中的CRTH2+T细胞没有增加。哮喘患者BAL中IL-4+和IL-13+T细胞表面CRTH2较干扰素-γ+T细胞显著升高(P&lt;0·001)。与干扰素-γ+T细胞相比,IL-4+/IL-13+T细胞优先表达CRTH2。然而,由于它们的数量很少,它们不太可能与哮喘的发病机制有重大关系。CRTH2拮抗作用可能不会减少T细胞在哮喘肺中的蓄积。
Mast cell-derived prostaglandin D2 (PGD2) is the major prostanoid found within the airway of asthmatics immediately following allergen challenge. PGD2 has been shown to have chemokinetic effects on eosinophils and T helper type 2 (Th2) cells in vitro. This occurs through the interaction of PGD2 with the G-protein-coupled chemokine receptor homologous molecule expressed on Th2 lymphocytes (CRTH2). The expression of CRTH2 has been shown to be highly selective for Th2 cells. Using flow cytometry we have studied the expression of CRTH2 on T cells in blood and bronchoalveolar lavage fluid in asthmatics and normal subjects. CRTH2 expression was confined to a small percentage of blood T cells in asthmatics (1·8% ± 0·2) and normal (1·6% ± 0·2) subjects. CRTH2 was enriched significantly on interleukin (IL)-4+/IL-13+ T cells compared to interferon (IFN)-γ+ T cells (P < 0·001). There was a small population of CRTH2+ T cells in the bronchoalveolar lavage (BAL) of asthmatics (2·3% ± 0·6) and normal subjects (0·3% ± 0·1), and there was a significant difference between the two groups (P < 0·05). There were similar amounts of PGD2 in the BAL of asthma and normal subjects. Within paired blood–BAL samples from the same subject there was no increase in CRTH2+ T cells in the BAL compared to blood in asthmatics. Enrichment of CRTH2 on IL-4+ and IL-13+ T cells compared to IFN-γ+ T cells was also seen in BAL from asthmatics (P < 0·001). CRTH2 is expressed preferentially by IL-4+/IL-13+ T cells compared to IFN-γ+ T cells. However, given their small numbers they are unlikely to have a significant involvement in the pathogenesis of asthma. CRTH2 antagonism may not diminish T cell accumulation in the asthmatic lung.
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