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Up-regulation of CC chemokine receptor 6 on tonsillar T cells and its induction by in vitro stimulation with α-streptococci in patients with pustulosis palmaris et plantaris

机译:脓疱病和足底脓疱病患者扁桃体T细胞CC趋化因子受体6的上调及其体外刺激α-链球菌的诱导

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摘要

Pustulosis palmaris et plantaris (PPP) is a tonsil-related disease; tonsillectomy is somewhat effective in treating the condition. However, the aetiological association between the tonsils and PPP has not yet been elucidated fully. Recently, some chemokines and chemokine receptors, including CC chemokine receptor (CCR) 4, CCR6 and CX chemokine receptor (CXCR) 3, have been reported to play important roles in the development of psoriasis, a disease related closely to PPP. In this study, we found that CCR6 expression on both tonsillar and peripheral blood T cells was up-regulated more intensively in PPP patients than in non-PPP patients (P < 0·001 for both), but CCR4 and CXCR3 expressions were not. In vitro stimulation with α-streptococcal antigen enhanced CCR6 expression significantly on tonsillar T cells in PPP patients (P < 0·05), but this was not observed in non-PPP patients. The chemotactic response of tonsillar T cells to the CCR6 ligand CC chemokine ligand (CCL) 20 was significantly higher in PPP patients than in non-PPP patients (P < 0·05). The percentage of CCR6-positive peripheral blood T cells decreased after tonsillectomy in PPP patients (P < 0·01); this decrease correlated with an improvement of skin lesions (P < 0·05, r = −0·63). The numbers of CCR6-positive cells and the expression of CCL20 were increased significantly in pathological lesions compared with non-pathological lesions in PPP skin (P < 0·01, P < 0·05 respectively). These results suggest that a novel immune response to α-streptococci may enhance CCR6 expression on T cells in tonsils and that CCR6-positive T cells may move to peripheral blood circulation, resulting in recruitment to target skin lesions expressing CCL20 in PPP patients. This may be one of the key roles in pathogenesis of the tonsil-related disease PPP.
机译:掌疱疹和足底脓疱病(PPP)是一种与扁桃体相关的疾病;扁桃体切除术在治疗该病方面有些有效。但是,扁桃体与PPP之间的病因学关联尚未完全阐明。最近,已经报道了一些趋化因子和趋化因子受体,包括CC趋化因子受体(CCR)4,CCR6和CX趋化因子受体(CXCR)3在与PPP密切相关的牛皮癣的发展中起着重要作用。在这项研究中,我们发现PPP患者的扁桃体和外周血T细胞上CCR6的表达比非PPP患者的CCR6的表达更强烈(两者均P <0·001),而CCR4和CXCR3的表达却没有。 α-链球菌抗原的体外刺激显着增强了PPP患者扁桃体T细胞的CCR6表达(P <0·05),但在非PPP患者中未观察到。 PPP患者的扁桃体T细胞对CCR6配体CC趋化因子配体(CCL)20的趋化反应显着高于非PPP患者(P <0·05)。 PPP患者扁桃体切除术后CCR6阳性外周血T细胞百分比降低(P <0·01);这种减少与皮肤病变的改善相关(P <0·05,r = −0·63)。与非病理性病变相比,PPP皮肤中CCR6阳性细胞的数量和CCL20的表达均显着增加(分别为P <0·01,P <0·05)。这些结果表明,对α-链球菌的新型免疫反应可能会增强扁桃体T细胞上CCR6的表达,而CCR6阳性T细胞可能会转移至外周血循环,从而招募新的靶点以表达PPP患者中的CCL20。这可能是扁桃体相关疾病PPP发病机理中的关键作用之一。

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