Possible association of proinflammatory cytokines including IL1β and TNFα with enhanced Th17 cell differentiation in patients with Behcet's disease.
Possible association of proinflammatory cytokines including IL1β and TNFα with enhanced Th17 cell differentiation in patients with Behcet's disease.
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包括 IL1β 和 TNFα 在内的促炎细胞因子可能与白塞病患者 Th17 细胞分化增强有关。
DOI：
10.1007/s10067-015-2966-2
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Suzuki N.
中科院分区：
文献类型：
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作者：
7.Shimizu J;Takai K;Takada E;Fujiwara N;Arimitsu N;Ueda Y;Wakisaka S;Suzuki T;Suzuki N.
我们已经报道了辅助性T 17型（Th 17）细胞在白塞病（BD）患者中增加。Th 17细胞在患者中如何增加仍然不清楚。我们在此分析了BD患者中T细胞是否优先分化为Th 17细胞以响应各种炎性细胞因子。BD患者体外培养2 d后，外源性白细胞介素（IL）23可维持较高的CD 4 + CD 45 RO + T细胞Th 17细胞频率，而正常人T细胞亚群对IL 23无应答。在新鲜分离的BD CD 4 + CD 45 RO + T细胞中IL 23受体阳性细胞频率与通过细胞内细胞因子染色评估的Th 17细胞频率相关。在用IL 23培养2天后，BD CD 4 + T细胞保留了IL 23受体表达水平与IL 17分泌程度之间的相关性（如Th 17细胞频率所示），而在正常个体中未注意到这种相关性。因此，在BD患者中，IL 23信号及其受体在短时间培养中诱导IL 17分泌（Th 17细胞频率）。我们用各种炎症细胞因子培养CD 4 + CD 45 RO − T细胞11天，以研究哪种细胞因子与患者中Th 17频率增强相关。与正常人相比，补充IL 1 β和肿瘤坏死因子（TNF）α以及IL 23后，BD患者的CD 4 + CD 45 RO − T细胞产生的IL 17显著增加。这些结果表明，促炎细胞因子，如IL 1 β，TNFα和IL 23，可能与BD患者中Th 17细胞的扩增有关。本研究已在大学医院医学信息网络-临床试验注册处（UMIN 000003806）注册。
We have reported that helper T type 17 (Th17) cells increased in patients with Behcet’s disease (BD). It remains obscure how Th17 cells increase in the patients. We here analyzed whether T cells preferentially differentiate into Th17 cells in response to various inflammatory cytokines in patients with BD. Exogenous interleukin (IL)23 sustained the higher Th17 cell frequencies of CD4+CD45RO+ T cells after a 2-day culture in vitro in patients with BD, whereas the T cell subpopulation of normal individuals did not respond to IL23 to sustain/increase Th17 cell frequencies. IL23 receptor positive cell frequencies in freshly isolated BD CD4+CD45RO+ T cells correlated with Th17 cell frequencies assessed by intracellular cytokine staining. After a 2-day culture with IL23, BD CD4+ T cells retained the correlation between IL23 receptor expression level and extent of IL17 secretion (as indicated by Th17 cell frequencies), whereas such correlation was not noted in normal individuals. IL23 signals with its receptor were thus suggested to induce IL17 secretion (Th17 cell frequencies) in a short-time culture in patients with BD. We cultured CD4+CD45RO− T cells for 11 days with various inflammatory cytokines to study which cytokine associated with the enhanced Th17 frequencies in the patients. IL17 production by CD4+CD45RO− T cells of BD patients increased significantly by the supplementation of IL1β and tumor necrosis factor (TNF)α, in addition to IL23, compared with that of normal individuals. These results suggest that proinflammatory cytokines, such as IL1β, TNFα, and IL23, may associate with the expansion of Th17 cells in patients with BD. This study was registered with the University Hospital Medical Information Network-Clinical Trials Registry (UMIN000003806).