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首页> 外文期刊>Journal of dermatological science >CXCL10 produced from hair follicles induces Th1 and Tc1 cell infiltration in the acute phase of alopecia areata followed by sustained Tc1 accumulation in the chronic phase
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CXCL10 produced from hair follicles induces Th1 and Tc1 cell infiltration in the acute phase of alopecia areata followed by sustained Tc1 accumulation in the chronic phase

机译:毛囊产生的CXCL10在斑秃的急性期诱导Th1和Tc1细胞浸润,然后在慢性期持续Tc1积累

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Background: Alopecia areata (AA) is an organ-specific and cell-mediated autoimmune disease. T lymphocytes densely surround lesional hair bulbs, which is histologically referred to as " swarm of bees" However, pathomechanisms of " swarm of bees" are still uncertain. Objective: We investigated the pathological mechanisms of " swarm of bees" , focusing on T-cell chemotaxis so that inhibition of chemotaxis may be strong candidate of novel treatments for AA. Methods: We investigate the expression of chemokine receptors on T cells obtained from peripheral blood mononuclear cells (PBMCs) and skin infiltrating cells in AA patients. In addition, real-time chemotaxis assay was also demonstrated. Results: In PBMCs, the frequency of CXCR3+CD4+ T cells (Th1) was significantly higher in acute-phase AA than in chronic-phase AA or healthy control, while CXCR3+CD8+ T cells (Tc1) were significantly increased in chronic-phase AA. In the skin lesions of acute-phase AA, CXCR3+CD4+ and CXCR3+CD8+ T cells infiltrated in the juxta-follicular area. In chronic-phase AA, CXCR3+CD8+ T cells dominated the infiltrate around hair bulbs, possibly contributing to the prolonged state of hair loss. Lymphocytes obtained from a lesional skin of acute-phase AA contained CXCR3+CD4+ and CXCR3+CD8+ T cells at higher percentages than those of PBMCs, suggesting preferential emigration from the blood. Immunohistochemical and real-time RT-PCR studies demonstrated that hair follicles of acute-phase AA expressed a high level of Th1-associated chemokine CXCL10. By chemotaxis assay, freshly isolated PBMCs from acute-phase AA patients had a strong velocity of chemotaxis toward CXCL10 with increased expression of F-actin. Conclusions: These results suggest that the increased production of CXCL10 from hair follicles induces preferential infiltrates of highly chemoattracted Th1 and Tc1 cells in the acute phase of AA, and Tc1 infiltration remains prolonged in the chronic phase.
机译:背景:斑秃(AA)是一种器官特异性和细胞介导的自身免疫性疾病。 T淋巴细胞密集地围绕病灶毛发鳞茎,在组织学上被称为“蜜蜂群”。但是,“蜜蜂群”的致病机理仍然不确定。目的:我们研究“蜂群”的病理机制,着眼于T细胞趋化性,从而抑制趋化性可能成为AA新疗法的有力候选者。方法:我们调查趋化因子受体在AA患者外周血单核细胞(PBMC)和皮肤浸润细胞中获得的T细胞上的表达。另外,还证实了实时趋化性测定。结果:在PBMC中,急性期AA的CXCR3 + CD4 + T细胞(Th1)的频率显着高于慢性期AA或健康对照组,而慢性期的CXCR3 + CD8 + T细胞(Tc1)的频率显着增加机管局。在急性期AA的皮肤病变中,CXCR3 + CD4 +和CXCR3 + CD8 + T细胞浸润在近卵泡区域。在慢性期AA中,CXCR3 + CD8 + T细胞主导了毛发周围的浸润,可能导致脱发时间延长。从急性期AA病变皮肤获得的淋巴细胞所含CXCR3 + CD4 +和CXCR3 + CD8 + T细胞的百分比高于PBMC,表明从血液中优先迁移。免疫组织化学和实时RT-PCR研究表明,急性期AA的毛囊表达高水平的Th1相关趋化因子CXCL10。通过趋化性测定,急性期AA患者新鲜分离的PBMC对CXCL10的趋化性很强,而F-肌动蛋白的表达增加。结论:这些结果表明,从毛囊中产生的CXCL10的增加会在机管局的急性期诱导高度化学吸引的Th1和Tc1细胞的优先浸润,而在慢性期Tc1的浸润仍会延长。

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