Endogenous programmed death ligand-1 restrains the development and onset of Sjӧgren's syndrome in non-obese diabetic mice.
Endogenous programmed death ligand-1 restrains the development and onset of Sjӧgren's syndrome in non-obese diabetic mice.
复制标题
内源性编程的死亡配体1限制了非肥胖糖尿病小鼠中Sjӧgren综合征的发育和发作。
DOI：
10.1038/srep39105
复制
发表时间：
2016-12-14
影响因子：
4.6
通讯作者：
Yu Q
中科院分区：
文献类型：
--
作者：
Zhou J;Jin JO;Kawai T;Yu Q
程序性死亡配体1 （PD-L1）通过参与共抑制受体程序性死亡-1下调各种免疫反应。Sjögren综合征（SS）患者唾液腺中PD-L1和程序性死亡-1的表达升高。本研究的目的是明确内源性PD-L1在非肥胖型糖尿病（NOD）小鼠模型中SS发病机制中的作用。我们通过在9天的时间内反复向6周龄雌性NOD/ShiLtJ小鼠腹腔注射阻断抗体来抑制内源性PD-L1功能。PD-L1阻断加速了颌下腺（SMG）中白细胞浸润和caspase-3的激活，抗核和抗m3毒蕈碱乙酰胆碱受体（M3R）自身抗体的产生和唾液分泌的损害，表明SS的加速发展和发病。PD-L1阻断的作用与SMG中T细胞和B细胞以及T辅助1细胞因子IFN-γ的增加有关。外源性IFN-γ局部作用于SMG导致唾液分泌受损，并伴有水通道蛋白5的下调和抗m3r自身抗体的增加。相反，中和IFN-γ可显著改善抗pd - l1处理NOD/ShiLtJ小鼠的唾液分泌和水通道蛋白5的表达。因此，内源性PD-L1通过抑制IFN-γ的产生，在一定程度上阻碍了NOD小鼠SS的发生和发展。
Programmed death-ligand 1 (PD-L1) down-modulates various immune responses by engaging the co-inhibitory receptor programmed death-1. Expression of PD-L1 and programmed death-1 is elevated in the salivary glands of patients with Sjögren’s syndrome (SS). The objective of this study is to define the role of endogenous PD-L1 in SS pathogenesis in non-obese diabetic (NOD) mouse model of this disease. We inhibited endogenous PD-L1 function by intraperitoneal administration of a blocking antibody to 6 week-old female NOD/ShiLtJ mice repeatedly during a 9-day period. PD-L1 blockade accelerated leukocyte infiltration and caspase-3 activation in the submandibular gland (SMG), production of antinuclear and anti-M3 muscarinic acetylcholine receptor (M3R) autoantibodies and impairment of saliva secretion, indicative of accelerated development and onset of SS. The effect of PD-L1 blockade was associated with increased T- and B cells and T helper 1 cytokine IFN-γ in the SMG. Local administration of exogenous IFN-γ to the SMG led to impaired salivary secretion accompanied by down-regulation of aquaporin 5 and an increase in anti-M3R autoantibodies. Conversely, neutralization of IFN-γ markedly improved salivary secretion and aquaporin 5 expression in anti-PD-L1-treated NOD/ShiLtJ mice. Hence, endogenous PD-L1 hinders the development and onset of SS in NOD mice, in part by suppressing IFN-γ production.
登录
查看更多内容
影响因子：
3
作者：
Klimatcheva E;Pandina T;Reilly C;Torno S;Bussler H;Scrivens M;Jonason A;Mallow C;Doherty M;Paris M;Smith ES;Zauderer M
通讯作者：
Zauderer M
影响因子：
3.7
作者：
Arellano-Garcia ME;Misuno K;Tran SD;Hu S
通讯作者：
Hu S
影响因子：
3.1
作者：
Beswick, Ellen J.;Pinchuk, Irina V.;Reyes, Victor E.
通讯作者：
Reyes, Victor E.
DOI：
10.1196/annals.1384.003
发表时间：
2007-01-01
期刊：
ORAL-BASED DIAGNOSTICS
影响因子：
--
作者：
Fox, Philip C.
通讯作者：
Fox, Philip C.
DOI：
10.1084/jem.20090847
发表时间：
2009-12-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Francisco LM;Salinas VH;Brown KE;Vanguri VK;Freeman GJ;Kuchroo VK;Sharpe AH
通讯作者：
Sharpe AH