Reduced expression of monocyte CD200R is associated with enhanced proinflammatory cytokine production in sarcoidosis.
Reduced expression of monocyte CD200R is associated with enhanced proinflammatory cytokine production in sarcoidosis.
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DOI：
10.1038/srep38689
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发表时间：
2016-12-08
影响因子：
4.6
通讯作者：
Hart SP
中科院分区：
文献类型：
--
作者：
Fraser SD;Sadofsky LR;Kaye PM;Hart SP
在结节病中，促炎细胞因子干扰素γ、肿瘤坏死因子和白细胞介素-6由肺和其他受影响组织中的单核细胞衍生的巨噬细胞和淋巴细胞释放。在单核细胞和巨噬细胞上表达的调节受体起抑制细胞因子产生的作用，并且调节受体的表达减少可因此促进组织炎症。本研究的目的是阐明调节受体在结节病患者血单核细胞中的作用。在健康对照组和未接受疾病改善治疗的患有结节病的白种人非吸烟患者中测量响应于全血刺激的细胞因子释放。通过流式细胞术测量调节分子IL-10 R、SIRP-α/β、CD 47、CD 200 R和CD 200 L的表达，并使用封闭抗体评估功能活性。与健康对照组相比，结节病患者的刺激全血和单核细胞产生更多的TNF和IL-6。52.9%的结节病患者的单核细胞CD 200 R低表达，而对照组为11.7%（p < 0.0001）。单核细胞CD 200 R表达低的患者产生更高水平的促炎细胞因子。在功能研究中，阻断CD 200轴增加了TNF和IL-6的产生。单核细胞上CD 200 R表达减少可能是结节病中单核细胞和巨噬细胞过度活化的一种机制。
In sarcoidosis, the proinflammatory cytokines interferon gamma, tumour necrosis factor and interleukin-6 are released by monocyte-derived macrophages and lymphocytes in the lungs and other affected tissues. Regulatory receptors expressed on monocytes and macrophages act to suppress cytokine production, and reduced expression of regulatory receptors may thus promote tissue inflammation. The aim of this study was to characterise the role of regulatory receptors on blood monocytes in patients with sarcoidosis. Cytokine release in response to stimulation of whole blood was measured in healthy controls and Caucasian non-smoking patients with sarcoidosis who were not taking disease modifying therapy. Expression of the regulatory molecules IL-10R, SIRP-α/β, CD47, CD200R, and CD200L was measured by flow cytometry, and functional activity was assessed using blocking antibodies. Stimulated whole blood and monocytes from patients with sarcoidosis produced more TNF and IL-6 compared with healthy controls. 52.9% of sarcoidosis patients had monocytes characterised by low expression of CD200R, compared with 11.7% of controls (p < 0.0001). Patients with low monocyte CD200R expression produced higher levels of proinflammatory cytokines. In functional studies, blocking the CD200 axis increased production of TNF and IL-6. Reduced expression of CD200R on monocytes may be a mechanism contributing to monocyte and macrophage hyper-activation in sarcoidosis.
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影响因子：
4.4
作者：
Cherwinski, HM;Murphy, CA;Phillips, JH
通讯作者：
Phillips, JH
影响因子：
5.4
作者：
Crawshaw A;Kendrick YR;McMichael AJ;Ho LP
通讯作者：
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影响因子：
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作者：
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通讯作者：
LINDAHLK.K
DOI：
10.1164/rccm.200603-402oc
发表时间：
2006-10-01
影响因子：
24.7
作者：
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通讯作者：
Barnathan, Elliot S.
影响因子：
3.8
作者：
DEGROOTE, D;ZANGERLE, PF;FRANCHIMONT, P
通讯作者：
FRANCHIMONT, P