Endothelial Cells Activated by Extracellular Histones Promote Foxp3(+) Suppressive Treg Cells In Vitro.
Endothelial Cells Activated by Extracellular Histones Promote Foxp3(+) Suppressive Treg Cells In Vitro.
复制标题
细胞外组蛋白激活内皮细胞促进Foxp3（+）抑制Treg细胞的体外研究
DOI：
10.3390/ijms23094527
复制
发表时间：
2022-04-20
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
当组蛋白从细胞核释放到细胞外间隙时，它们被广泛认为是促炎介质。然而，它们对内皮细胞免疫原性的影响尚不清楚。为了研究重组组蛋白对血管内皮细胞表型的影响，人微血管内皮细胞1(HMEC1)被暴露于重组组蛋白中。然后，我们在体外研究了与内皮细胞相互作用三天后的CD4+-T淋巴细胞亚群的分化，观察到组蛋白处理的内皮细胞分化为表达人类白细胞抗原DR(人类白细胞抗原DR)和细胞毒性T淋巴细胞相关蛋白4(CTLA4)的抑制性FoxP3+T调节亚群。抑制Toll样受体4(TLR4)可显著抑制这些Treg细胞的增殖。此外，阻断IL-6和ICAM-1可显著抑制Tregs的扩增，提示存在依赖IL-6和ICAM-1的途径。因此，除了炎症作用外，细胞外组蛋白可能通过对内皮细胞的作用而诱导免疫抑制Treg细胞数量的增加。需要进一步的研究来评估组蛋白通过激活内皮细胞增加外周血抑制性Treg对免疫抑制的影响。
Histones are widely recognized as pro-inflammatory mediators upon their release from the nucleus into the extracellular space. However, their impact on endothelial cell immunogenicity is unknown. Endothelial cells, Human Microvascular Endothelial cells 1 (HMEC1), have been exposed to recombinant histones in order to study their effect on the endothelial phenotype. We then studied the differentiation of CD4+-T lymphocytes subpopulations after three days of interaction with endothelial cells in vitro and observed that histone-treated endothelial cells differentiate a suppressive FoxP3+ T regulator subpopulation that expressed Human Leucocyte Antigen DR (HLA-DR) and Cytotoxic T-Lymphocyte-Associated protein 4 (CTLA4). Toll-Like Receptor 4 (TLR4) inhibition significantly decreased the expansion of these Treg cells. Moreover, blockade of Interleukin (IL)-6 and Intercellular Adhesion Molecule (ICAM)-1 in cocultures significantly decreased the expansion of Tregs, suggesting an IL-6 and ICAM-1 dependent pathway. Thus, beyond their inflammatory effects, extracellular histones may induce an increase of immunosuppressive Treg population via their action on endothelial cells. Further studies are needed to evaluate the impact on immunosuppression of an increase of peripheral suppressive Treg via endothelial cell activation by histones in vivo.
登录
查看更多内容
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
4.4
作者：
Baecher-Allan, Clare;Wolf, Elizabeth;Haller, David A.
通讯作者：
Haller, David A.
影响因子：
13.6
作者：
Hagenstein, Julia;Melderis, Simon;Steinmetz, Oliver M.
通讯作者：
Steinmetz, Oliver M.
DOI：
10.1007/978-1-61737-979-6_2
发表时间：
2011
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Collison, Lauren W;Vignali, Dario A A
通讯作者：
Vignali, Dario A A
PD-L1 的过度表达与人类肝细胞癌的肿瘤侵袭性和术后复发显着相关。
影响因子：
11.5
作者：
Gao, Qiang;Wang, Xiao-Ying;Fan, Jia
通讯作者：
Fan, Jia