An activated set point of T-cell and monocyte inflammatory networks in recent-onset schizophrenia patients involves both pro- and anti-inflammatory forces
An activated set point of T-cell and monocyte inflammatory networks in recent-onset schizophrenia patients involves both pro- and anti-inflammatory forces
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DOI：
10.1017/s1461145710001653
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发表时间：
2011-07-01
影响因子：
4.8
通讯作者：
Drexhage, Hemmo A.
中科院分区：
文献类型：
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作者：
Drexhage, Roosmarijn C.;Hoogenboezem, Thomas A.;Drexhage, Hemmo A.
我们最近在60%的新发精神分裂症（SCZ）患者的单核细胞中描述了促炎基因表达特征。在这里，我们研究了t细胞系统是否也处于促炎状态。对26例新近发病的SCZ患者（其中19例单核细胞的炎症基因表达特征已被确定）和年龄/性别匹配的健康对照进行了详细的荧光激活细胞分选（FACS）分析，例如CD3(+) CD25(+) T细胞、ifn - γ(+)、IL-4（+）、IL-17A(+) （CD4(+)）淋巴细胞和CD4(+) CD25（高）FoxP3（+）调节性T细胞。多种相关的t细胞因子，如sCD25， ifn - γ， IL-17A和IL-4，通过多重检测测定血清中。我们检测到：(a)患者中不仅有较高百分比的促炎倾向单核细胞、活化的CD3(+) CD25(+) T细胞和促炎Th17细胞，而且有较高百分比的抗炎CD4(+) CD25（高）FoxP3（+）调节性T细胞和IL-4（+）淋巴细胞；(b)这种活化的t细胞设定点反映在sCD25的血清水平显著升高；(c)含IL-4（+）淋巴细胞的上调主要见于单核细胞促炎设定点的患者；(d)无论单核细胞的促炎状态如何，患者的调节性t细胞和th17细胞数量都较高。我们的数据不支持t细胞系统在最近发病的SCZ中处于简单的促炎状态的概念，但确实表明单核细胞和t细胞网络被激活，并涉及促炎和抗炎力量。这表明在激活的炎症系统内进行控制。
We recently described a pro-inflammatory gene expression signature in the monocytes of 60% of patients with recent-onset schizophrenia (SCZ). Here we investigated whether the T-cell system is also in a pro-inflammatory state. A detailed fluorescence-activated cell sorting (FACS) analysis, e. g. of CD3(+) CD25(+) T cells, IFN-gamma(+), IL-4(+), IL-17A(+) (CD4(+)) lymphocytes and CD4(+) CD25(high)FoxP3(+) regulatory T cells, was performed on peripheral blood of 26 patients with recent-onset SCZ (in 19 of whom the inflammatory gene expression signature of the monocyte had been determined) and in age-/gender-matched healthy controls. Various relevant T-cell cytokines, e.g. sCD25, IFN-gamma, IL-17A and IL-4, were measured in serum by a multiplex assay. We detected : (a) not only higher percentages of pro-inflammatory-prone monocytes, activated CD3(+) CD25(+) T cells and pro-inflammatory Th17 cells in patients, but also higher percentages of anti-inflammatory CD4(+) CD25(high)FoxP3(+) regulatory T cells and IL-4(+) lymphocytes; (b) that this activated T-cell set point was reflected in significantly raised serum levels of sCD25; (c) that the up-regulation of IL-4(+)-containing lymphocytes was predominantly found in patients characterized by a monocyte pro-inflammatory set point; and (d) that regulatory T-cell and Th17-cell numbers were higher in patients irrespective of the pro-inflammatory state of the monocytes. Our data do not support the concept that the T-cell system is in a simple pro-inflammatory state in recent-onset SCZ, but do show that the monocyte and T-cell networks are activated and involve both pro-and anti-inflammatory forces. This suggests control within an activated inflammatory system.