Predominance of activated, clonally expanded T helper type 17 cells within the CD4+T cell population in psoriatic lesions
Predominance of activated, clonally expanded T helper type 17 cells within the CD4+T cell population in psoriatic lesions
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DOI：
10.1111/cei.12086
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发表时间：
2013-07-01
影响因子：
4.6
通讯作者：
Ormerod, A. D.
中科院分区：
文献类型：
--
作者：
Lewis, B. J.;Rajpara, S.;Ormerod, A. D.
最近的证据表明 17 型辅助性 T (Th17) 子集是银屑病发病机制的关键，但病变中这种类型的细胞仍有待充分表征。在这里，我们从银屑病患者的皮损活检和配对外周血样本中离体分离、计数、功能测试和克隆分型 CD4+ Th 细胞群。 Th17 细胞在所有患者的病变中显着过量，占 CD4+ Th 细胞的 49-93%，而血液中这一比例为 3-18%。大多数病变 Th17 细胞无需进一步刺激即可离体产生白细胞介素 (IL)-17A，并表达激活细胞或记忆细胞的 CD45RO+ 表型特征。与外周血相比，病变中天然的[CD25hi叉头盒蛋白3 (FoxP3+)]调节性T细胞没有增加，但一些患者的活检组织中诱导的IL-10+调节性T细胞数量有所富集。病变 Th17 细胞在 T 细胞受体 V 链使用方面表现出偏差，表明抗原的特异性扩增。治疗挑战是克服银屑病皮损中绝大多数此类抗原特异性 Th17 细胞的主导地位。
Recent evidence points to the T helper type 17 (Th17) subset as key in the pathogenesis of psoriasis, but cells of this type in lesions remain to be fully characterized. Here we isolated, enumerated, functionally tested and clonotyped the CD4+ Th cell population ex vivo from lesional biopsies and paired peripheral blood samples from psoriasis patients. Th17 cells were over-represented dramatically in lesions from all patients, representing 49-93% of CD4+ Th cells compared with 3-18% in blood. Most lesional Th17 cells produced interleukin (IL)-17Aex vivo without further stimulation and expressed the CD45RO+ phenotype characteristic of activated or memory cells. There was no increase in natural' [CD25hiforkhead box protein 3 (FoxP3+)] regulatory T cells in lesions versus peripheral blood, but there was enrichment of induced' IL-10+ regulatory T cell numbers in biopsies from some patients. The lesional Th17 cells exhibited a bias in T cell receptor V chain usage, suggestive of specific expansion by antigen. The therapeutic challenge is to overcome the dominance of overwhelming numbers of such antigen-specific Th17 cells in psoriatic lesions.