Down-regulated NOD2 by immunosuppressants in peripheral blood cells in patients with SLE reduces the muramyl dipeptide-induced IL-10 production.
Down-regulated NOD2 by immunosuppressants in peripheral blood cells in patients with SLE reduces the muramyl dipeptide-induced IL-10 production.
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DOI：
10.1371/journal.pone.0023855
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Tam LS
中科院分区：
文献类型：
--
作者：
Yu SL;Wong CK;Wong PT;Chen DP;Szeto CC;Li EK;Tam LS
Toll样受体等模式识别受体在系统性红斑狼疮（SLE）患者外周血单个核细胞（PBMC）中异常表达，发挥免疫病理作用。我们研究了PRR核苷酸结合寡聚化结构域（NOD 2）在SLE中的表达和功能。采用流式细胞术分析SLE患者和健康对照（HC）中T、B淋巴细胞、单核细胞、髓样树突状细胞（mDC）和浆细胞样树突状细胞（pDC）中NOD 2的表达。使用流式微珠阵列评估NOD 2激动剂胞壁酰二肽（MDP）刺激后PBMC的细胞因子的离体产生。在免疫抑制剂初治的SLE患者中观察到单核细胞中NOD 2的过度表达，并且与较长的疾病持续时间呈正相关。免疫抑制治疗是下调CD 8 + T细胞、单核细胞、mDC和pDC中NOD 2表达的独立解释变量。与HC相比，未使用免疫抑制剂的患者和尽管使用免疫抑制剂但仍患有活动性疾病的患者的细胞因子（IL-6，IL-8和IL-10）的体外基础产生显著增加。在MDP刺激后，与HC相比，未经免疫抑制剂治疗的非活动性疾病患者和尽管接受免疫抑制剂治疗但仍患有活动性疾病的患者PBMC中细胞因子（IL-1β）的相对诱导（%）显著增加。与免疫抑制剂初治患者和HC相比，免疫抑制剂使用与非活动性疾病患者中IL-10的基础产生和MDP诱导的相对诱导（%）降低相关。在免疫抑制剂初治的SLE患者中，细菌暴露可能增加单核细胞中NOD 2的表达，这随后可导致PBMC异常活化以产生促炎细胞因子，这暗示了SLE的免疫病理机制中对细胞外病原体的先天免疫应答。免疫抑制剂治疗可能下调SLE患者CD 8 + T淋巴细胞、单核细胞和DC中NOD 2的表达，随后IL-10减少，有助于调节SLE的免疫病理机制，但以增加细菌感染的风险为代价。
Pattern recognition receptors (PRRs) such as Toll-like receptors are aberrantly expressed of peripheral blood mononuclear cells (PBMCs) in systemic lupus erythematosus (SLE) patients, for playing immunopathological roles. We investigated the expression and function of the PRR nucleotide-binding oligomerization domain (NOD2) in SLE. NOD2 expression in T, B lymphocytes, monocytes, myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) was assessed in SLE patients and healthy controls (HCs) using flow cytometric analysis. Ex vivo production of cytokines from PBMCs upon NOD2 agonist muramyl dipeptide (MDP) stimulation was assessed using Cytometric Bead Array. Over-expression of NOD2 in monocytes was observed in immunosuppressant naïve SLE patients, and was positively associated with longer disease duration. Immunosuppressive therapy was an independent explanatory variable for downregulating NOD2 expression in CD8+ T, monocytes, mDCs and pDCs. Ex vivo basal productions of cytokines (IL-6, IL-8 and IL-10) were significantly increased in immunosuppressant naïve patients and patients with active disease despite immunosuppressants compared with HCs. Upon MDP stimulaiton, relative induction (%) of cytokines (IL-1β) from PBMC was significantly increased in immunosuppressant naïve patients with inactive disease, and patients with active disease despite immunosuppressant treatment compared with HCs. Immunosuppressant usage was associated with a decreased basal production and MDP induced relative induction (%) of IL-10 in patients with inactive disease compared with immunosuppressant naïve patients and HCs. Bacterial exposure may increase the NOD2 expression in monocytes in immunosuppressant naïve SLE patients which can subsequently lead to aberrant activation of PBMCs to produce proinflammatory cytokines, implicating the innate immune response for extracellular pathogens in the immunopathological mechanisms in SLE. Immunosuppressant therapy may downregulate NOD2 expression in CD8+ T lymphocytes, monocytes, and DCs in SLE patients which subsequently IL-10 reduction, contributing towards the regulation of immunopathological mechanisms of SLE, at the expense of increasing risk of bacterial infection.
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影响因子：
2.7
作者：
Khan, Niamat;Summers, Colin W.;Arkwright, Peter D.
通讯作者：
Arkwright, Peter D.
中国汉族人群的全基因组关联研究确定了系统性红斑狼疮的九个新易感位点
影响因子：
30.8
作者：
Han, Jian-Wen;Zheng, Hou-Feng;Zhang, Xue-Jun
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Zhang, Xue-Jun
6q23 上 TNFAIP3 附近的遗传变异与系统性红斑狼疮相关。
影响因子：
30.8
作者：
Graham, Robert R.;Cotsapas, Chris;Davies, Leela;Hackett, Rachel;Lessard, Christopher J.;Leon, Joanlise M.;Burtt, Noel P.;Guiducci, Candace;Parkin, Melissa;Gates, Casey;Plenge, Robert M.;Behrens, Timothy W.;Wither, Joan E.;Rioux, John D.;Fortin, Paul R.;Graham, Deborah Cunninghame;Wong, Andrew K.;Vyse, Timothy J.;Daly, Mark J.;Altshuler, David;Moser, Kathy L.;Gaffney, Patrick M.
通讯作者：
Gaffney, Patrick M.
DOI：
10.1084/jem.170.6.2081
发表时间：
1989-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fiorentino DF;Bond MW;Mosmann TR
通讯作者：
Mosmann TR
DOI：
10.1002/art.20837
发表时间：
2004-12-15
期刊：
ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH
影响因子：
--
作者：
Doria, A;Ghirardello, A;Cutolo, M
通讯作者：
Cutolo, M