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T follicular helper cell-mediated IL-21 production suppresses FOXP3 expression of T follicular regulatory-like cells in diffuse large B cell lymphoma patients.
Human Immunology ( IF 3.1 ) Pub Date : 2020-06-10 , DOI: 10.1016/j.humimm.2020.05.008
Xiaomei Ma 1 , Jie Zha 2 , Jixiang He 3 , Longtian Chen 1 , Jianqing Huang 1 , Weihao Wu 1 , Pan Tian 1 , Bao-Hua Qian 4 , Lian Yu 1 , Yirong Jiang 3 , Bing Xu 2
Affiliation  

Based on CD25 expression, T follicular helper cells (Tfh) could be divided into T follicular regulatory (Tfr)-like subset (CD25+CD4+CXCR5+) and CD25 Tfh subset (CD25CD4+CXCR5+). Patients with diffuse large B cell lymphoma (DLBCL) display high level of Tfr-like cells in blood and tumor. This Tfr-like subset could suppress CD8 T cell response while promote tumor cell proliferation. In this study, we investigated the transcription factors and regulatory elements associated with Tfr-like cells in DLBCL patients. Both circulating and tumor-infiltrating Tfr-like cells presented slightly higher Blimp-1 expression and significantly higher Foxp3 expression than the CD25 Tfh subset. As the IL-2 receptor, CD25 could be moderately upregulated in stimulated CD25 Tfh cells. However, stimulated CD25 Tfh cells could not upregulate Foxp3, indicating that the distinction between Foxp3-low CD25CXCR5+CD4+ T cells and Foxp3-high CD25+CXCR5+CD4+ T cells was not due to differences in stimulation status. Regarding cytokine production, while both Tfr-like and CD25 Tfh cells upregulated IL-21 and IL-10 during stimulation, the CD25 Tfh cells presented significantly higher IL-21 and lower IL-10 expression than the Tfr-like cells, and the TGF-β expression was only increased in Tfr-like cells. Interestingly, IL-21 secreted from CD25 Tfh cells negatively regulated the expression of Foxp3 and IL-10 of autologous Tfr-like cells. Together, these results demonstrated that the Tfr-like and CD25 Tfh subsets of circulating Tfh cells presented different functions and should be investigated separately.



中文翻译:

T滤泡辅助细胞介导的IL-21产生抑制了弥漫性大B细胞淋巴瘤患者T滤泡调节样细胞的FOXP3表达。

根据CD25的表达,T卵泡辅助细胞(Tfh)可分为T卵泡调节(Tfr)样亚群(CD25 + CD4 + CXCR5 +)和CD25 - Tfh亚群(CD25 - CD4 + CXCR5 +)。弥漫性大B细胞淋巴瘤(DLBCL)患者在血液和肿瘤中显示高水平的Tfr样细胞。这种类似Tfr的子集可以抑制CD8 T细胞反应,同时促进肿瘤细胞的增殖。在这项研究中,我们调查了DLBCL患者中与Tfr样细胞相关的转录因子和调控元件。与CD25 - Tfh亚群相比,循环的Tfr样细胞和肿瘤浸润的Tfr样细胞均表现出稍高的Blimp-1表达和Foxp3表达。作为IL-2受体,CD25在受刺激的CD25 - Tfh细胞中可能被适度上调。但是,刺激的CD25 - Tfh细胞不能上调Foxp3,表明Foxp3-low CD25 - CXCR5 +之间的区别CD4 + T细胞和Foxp3高CD25 + CXCR5 + CD4 + T细胞不是由于刺激状态的差异。关于细胞因子的产生,虽然Tfr样和CD25 - Tfh细胞在刺激过程中均上调IL-21和IL-10,但CD25 - Tfh细胞比Tfr样细胞表现出更高的IL-21和更低的IL-10表达。 TGF-β表达仅在Tfr样细胞中增加。有趣的是,从CD25 - Tfh细胞分泌的IL-21会负面调节自体Tfr样细胞的Foxp3和IL-10的表达。总之,这些结果表明,总和生育率样和CD25 - 循环Tfh细胞的Tfh子集表现出不同的功能,应单独研究。

更新日期:2020-08-15
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