Human IL-21+IFN-γ+CD4+ T cells in nasal polyps are regulated by IL-12.

Human IL-21+IFN-γ+CD4+ T cells in nasal polyps are regulated by IL-12.
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鼻息肉中的人 IL-21( )IFN-gamma( )CD4( ) T 细胞受 IL-12 调节

DOI:
10.1038/srep12781
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发表时间:
2015-08-04
期刊:
影响因子:
4.6
通讯作者:
Wu C
Wu C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Xiao L;Jia L;Zhang Y;Yu S;Wu X;Yang B;Li H;Wu C

文献摘要

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在前期的研究中,我们发现鼻息肉(NPs)中IL-21的水平显著升高,并且与息肉的大小和复发相关。然而,IL-21的细胞来源以及IL-21在NP组织中的调控尚不清楚。在本研究中,我们从NP组织、钩突组织和NP患者外周血中分离淋巴细胞。通过流式细胞术分析细胞的细胞表面标志物、细胞因子和转录因子。结果表明,NP组织中IL-21的表达主要为CD 4 + T细胞,且大多数产生IL-21的CD 4 + T细胞同时表达IFN-γ或IL-17 A。NP组织中的IL-21+IFN-γ+ CD 4 + T细胞表现出Tfh和Th 1细胞的特征,其共表达的CXCR 5、ICOS、PD-1、Bcl-6和T-bet的量显著高于IL-21+IFN-γ− CD 4 + T细胞(p < 0.05)。用IL-12处理NP组织中的淋巴细胞可增加IL-21和IFN-γ的产生,尤其是IL-21+IFN-γ+ CD 4 + T细胞的频率(p < 0.05)。IL-12的阻断抑制了IL-21和IFN-γ的产生(p < 0.05)。提示IL-12可促进NP组织中IL-21+IFN-γ+ CD 4 + T细胞的产生,同时具有Tfh和Th 1细胞的特征。
In the previous study, we found that the levels of IL-21 in nasal polyps (NPs) were significantly increased and associated with polyp size and recurrence. However, it is unclear that the cell source of IL-21 and the regulation of IL-21 in NP tissues. In the present study, we isolated the lymphocytes from NP tissues, uncinate tissues and peripheral blood of patients with NPs. The cells were analyzed for cell surface markers, cytokines and transcriptional factors by flow cytometry. The results indicated that CD4+ T cells were the major IL-21-exprssing cells in NP tissues and the majority of IL-21 producing CD4+ T cells co-expressed IFN-γ or IL-17A. IL-21+IFN-γ+CD4+ T cells in NP tissues exhibited the features of both Tfh and Th1 cells which co-expressed significantly higher amount of CXCR5, ICOS, PD-1, Bcl-6 and T-bet than did IL-21+IFN-γ−CD4+ T cells (p < 0.05). Treatment of the lymphocytes from NP tissues with IL-12 enhanced the production of IL-21 and IFN-γ, especially the frequency of IL-21+IFN−γ+CD4+ T cells (p < 0.05). The blockade of IL-12 inhibited the production of IL-21 and IFN-γ (p < 0.05). These findings indicated that IL-12 positively enhanced the generation of IL-21+IFN-γ+CD4+ T cells having the features of both Tfh and Th1 cells in NP tissues.