Enhanced Proliferation and Activation of Peripheral Blood Mononuclear Cells in Patients with Psoriasis Vulgaris Mediated by Streptococcal Antigen with Bacterial DNA
Enhanced Proliferation and Activation of Peripheral Blood Mononuclear Cells in Patients with Psoriasis Vulgaris Mediated by Streptococcal Antigen with Bacterial DNA
复制标题
DOI：
10.1038/jid.2009.153
复制
发表时间：
2009-11-01
影响因子：
6.5
通讯作者：
Zheng, Jie
中科院分区：
文献类型：
--
作者：
Cai, Yi-Hua;Lu, Zhi-Yong;Zheng, Jie
链球菌感染被认为与银屑病有密切的关系，尽管链球菌DNA的致病作用尚不完全清楚。为了更清楚地了解这些动力学，我们研究了链球菌DNA对银屑病患者淋巴细胞增殖和激活以及细胞因子分泌的影响。银屑病患者外周血单个核细胞(PBMC)在链球菌抗原(SA)刺激下的增殖反应明显高于健康人。值得注意的是，经DNase-I处理的SA处理后，这种促进PBMCs增殖的作用减弱。不含核酸(非核酸SA，Non-NASA)的SA刺激后，患者外周血T细胞表面CD69的表达水平，包括皮肤归巢淋巴细胞、皮肤淋巴细胞相关抗原阳性T细胞和PBMC分泌的干扰素-α的水平也比未经处理的SA刺激时降低。但经SA或非NASA刺激后，B细胞表面活化标志物CD86的表达水平以及干扰素-γ和肿瘤坏死因子-α的分泌均无明显变化。有趣的是，银屑病患者减弱的T细胞活化和干扰素-α的分泌在非NASA与合成CpG-A联合刺激时可以重建，但当与合成CpG-B联合刺激时不能重建。这项研究证明了SA，特别是链球菌DNA在银屑病发病机制中的完整功能。
Streptococcal infection is believed to have an intimate relationship with psoriasis, although the pathogenic role of streptococcal DNA is not fully understood. To gain a clearer understanding of these dynamics, we investigated the effect of streptococcal DNA on lymphocyte proliferation and activation as well as cytokine secretion in psoriasis. Peripheral blood mononuclear cells (PBMCs) from psoriatic patients had higher proliferative responses upon stimulation by streptococcal antigen (SA) when compared with those from healthy individuals. Strikingly, this enhanced proliferation of PBMCs was attenuated after administration of SA treated with DNase-I. In addition, CD69 expression levels on T cells, including skin-homing lymphocyte cutaneous lymphocyte-associated antigen positive T cells, and IFN-alpha secretion by PBMCs were also attenuated in patients after stimulation with SA without nucleic acid (non-nucleic acid SA, non-NASA) compared with stimulation with untreated SA. However, activation marker CD86 expression levels on B cells as well as the secretion of IFN-gamma and tumor necrosis factor (TNF)-alpha following stimulation with SA or non-NASA were not significantly altered. Interestingly, the attenuated T-cell activation and IFN-alpha secretion in psoriatic patients could be reconstituted when stimulated by non-NASA combined with synthetic CpG-A, but not when combined with synthetic CpG-B. This study demonstrates the integral function of SA, particularly streptococcal DNA, in the pathogenesis of psoriasis.