Calcitonin gene-related peptide modulates interleukin-13 in circulating cutaneous lymphocyte-associated antigen-positive T cells in patients with atopic dermatitis
Calcitonin gene-related peptide modulates interleukin-13 in circulating cutaneous lymphocyte-associated antigen-positive T cells in patients with atopic dermatitis
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DOI：
10.1111/j.1365-2133.2009.09318.x
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发表时间：
2009-09-01
影响因子：
10.3
通讯作者：
Santamaria-Babi, L. F.
中科院分区：
文献类型：
--
作者：
Antunez, C.;Torres, M. J.;Santamaria-Babi, L. F.
背景神经肽（NPs）可能通过调节免疫应答和促进免疫系统与神经系统之间的相互作用在特应性皮炎（AD）的发病机制中发挥重要作用。目的评估NPs对皮肤记忆T细胞[皮肤淋巴细胞相关抗原（LA-DR）]中白细胞介素（IL）-13和干扰素（IFN）-γ产生及活化标志物HLA-DR表达的影响。方法在有和无不同NP、降钙素基因相关肽（CGRP）、生长抑素（SOM）和P物质（SP）存在的情况下培养细胞。结果CGRP可使AD患者外周血单个核细胞产生IL-13（P < 0 0 5），而SOM和SP对IL-13产生无明显影响，AD患者CGRP受体表达低于对照组（P <0 0 5）。与对照组比较，AD患者记忆T细胞中CLA + T细胞IL-13和HLA-DR表达均显著增加（P <0 0 5），而CLA+ T细胞中IL-13和HLA-DR表达均无明显变化（P> 0 0 5）。具有较高IL-13产生的患者是具有较高总IgE和所涉及的皮肤面积百分比的患者。结论CGRP对CLA+ T细胞的Th 2型免疫调节作用可能与AD患者临床症状加重有关。
Background Neuropeptides (NPs) may play an important role in the pathogenesis of atopic dermatitis (AD) by regulating immune responses and contributing to the cross-talk between the immune and nervous systems.Objectives To assess the ability of NPs to influence interleukin (IL)-13 and interferon (IFN)-gamma production and the expression of the activation marker HLA-DR in skin memory T cells [cutaneous lymphocyte-associated antigen (CLA)+ T cells] from patients with AD with severe, chronic lesions and intense pruritus, and from nonatopic controls.Methods Cells were cultured in the presence and absence of different NPs, calcitonin gene-related peptide (CGRP), somatostatin (SOM) and substance P (SP). IL-13 and IFN-gamma production and HLA-DR expression were measured in both CLA+ and CLA) T-cell subsets by flow cytometry.Results CGRP increased IL-13 production in peripheral blood mononuclear cells from patients with AD (P < 0 05), with no changes detected in the presence of SOM or SP. These patients with AD had a lower expression of CGRP receptor compared with controls (P < 0 05). Memory T cells incubated with CGRP also showed an increase in IL-13 (P < 0 05) and HLA-DR (P < 0 05) in CLA+ T cells from patients with AD compared with controls, but not in CLA) T cells. Patients with a higher production of IL-13 were those with higher total IgE and percentage of skin area involved. Furthermore, the IL-13/IFN-gamma ratio was increased in patients with AD after cells were cultured with CGRP (P < 0 05).Conclusions Our results suggest an immunomodulatory role of CGRP towards a Th2 pattern in CLA+ T cells, which may contribute to exacerbating clinical symptoms in patients with AD.