CCR4+ Skin-Tropic Phenotype as a Feature of Central Memory CD8+ T Cells in Healthy Subjects and Psoriasis Patients
CCR4+ Skin-Tropic Phenotype as a Feature of Central Memory CD8+ T Cells in Healthy Subjects and Psoriasis Patients
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DOI：
10.3389/fimmu.2020.00529
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发表时间：
2020-04-03
影响因子：
7.3
通讯作者：
Reali, Eva
中科院分区：
文献类型：
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作者：
Casciano, Fabio;Diani, Marco;Reali, Eva
趋化因子受体CCR4已经成为一种皮肤归巢分子，对T细胞从血液到真皮的迁移非常重要。根据我们之前对银屑病患者的数据，CCR4(+)记忆T细胞可能是皮肤和血液之间的循环群体。在此，我们将注意力集中在记忆T细胞分化的不同阶段中CCR4和亲皮肤分子的表达。我们分析了CD8(+)和CD4(+)、CD45RA(-)、CCR7(+)(T-CM)和CD45RA(-)CCR7(-)(T-EM)细胞中趋化因子受体的分布。根据CD62L的表达进一步划分亚群，并评估皮肤归巢分子CLA(皮肤淋巴细胞抗原)亚群之间的分布。从21名健康人和24名银屑病患者分离的外周血单核细胞进行了表征。结果表明：(1)皮肤归巢CCR4主要表达于T-CM细胞，(2)CCR4(+)T-CM细胞也表达高水平的CLA，(3)分化程度较高的T-EM表达CXCR3和CCR5，而CCR4和CLA表达较低。这表明记忆T细胞分化的进展阶段具有截然不同的趋化因子受体模式，CD8(+)T-CM表现出明显的趋皮性表型CLA(+)和CCR4(+)。在正常人和银屑病患者中，T-CM和T-EM细胞具有不同的亲皮肤表型。然而，患者显示CD8(+)T-CM细胞的循环群体扩大，表型为CCR4(+)CXCR3(+)，这可能在银屑病的病理生理中发挥作用，并可能在疾病复发中发挥作用。
The chemokine receptor CCR4 has emerged as a skin-homing molecule important for the migration of T cells from the blood to the dermis. From our previous data on psoriasis patients, CCR4(+) memory T cells emerged as a putative recirculating population between skin and blood. Here we focused our attention on the expression of CCR4 and skin-tropic molecules in the different stages of memory T cell differentiation. We analyzed the chemokine receptor profile in CD8(+) and CD4(+) CD45RA(-)CCR7(+) (T-CM) and CD45RA(-)CCR7(-) (T-EM) cells. Subpopulations were further divided on the basis of CD62L expression, and the distribution among the subsets of the skin-homing molecule CLA (Cutaneous Lymphocyte Antigen) was evaluated. The characterization was performed on peripheral blood mononuclear cells isolated from 21 healthy subjects and 24 psoriasis patients. The results indicate that (i) the skin-homing CCR4 marker is mainly expressed in T-CM cells, (ii) CCR4(+) T-CM cells also express high level of CLA and that (iii) the more differentiated phenotype T-EM expresses CXCR3 and CCR5 but lower level of CCR4 and CLA. This indicates that progressive stages of memory T cell differentiation have profoundly different chemokine receptor patterns, with CD8(+) T-CM displaying a marked skin-tropic phenotype CLA(+)CCR4(+). Differential skin-tropic phenotype between T-CM and T-EM cells was observed in both healthy subjects and psoriasis patients. However, patients showed an expanded circulating population of CD8(+) T-CM cells with phenotype CCR4(+)CXCR3(+) that could play a role in the pathophysiology of psoriasis and possibly in disease recurrence.