Paraoxonase 1 knockout rats have impaired T cell development at the CD4/CD8 double-negative to double-positive transition stage.
Paraoxonase 1 knockout rats have impaired T cell development at the CD4/CD8 double-negative to double-positive transition stage.
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对氧磷酶 1 敲除大鼠在 CD4/CD8 双阴性到双阳性过渡阶段的 T 细胞发育受损
DOI：
10.1038/s41598-018-32780-w
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发表时间：
2018-09-27
影响因子：
4.6
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Bai L;Shi G;Ma Y;Zhang L;Guan F;Zhang X;Xu Y;Chen H;Zhang L
对氧磷酶1（PON 1）是一种高密度脂蛋白相关酶，具有多种生理活性。以往的研究表明，PON 1在心血管系统中发挥抗炎作用，但其在造血和适应性免疫中的作用尚未阐明。为了研究PON 1对免疫系统的影响，我们使用CRISPR/Cas9系统产生了PON 1敲除（PON 1-/-）大鼠。PON 1 −/−大鼠的胸腺比野生型（PON 1 +/+）大鼠的胸腺小。此外，对胸腺细胞发育的分析显示，PON 1 −/−大鼠外周血和胸腺中的总T细胞数量减少，CD 4+、CD 8+和双阳性T细胞减少。这可能是由于阻断了T细胞从双阴性阶段向双阳性阶段的转变。我们还发现p38 MAPK磷酸化的激活导致PON−/−大鼠中细胞凋亡增加和T细胞发育缺陷。因此，我们的研究结果表明，PON 1作为一种新的调节T细胞发育的功能。
Paraoxonase 1 (PON1) is a high-density lipoprotein-associated enzyme that performs multiple physiological activities. Previous studies suggest that PON1 plays an anti-inflammatory role in the cardiovascular system, although its roles in hematopoiesis and adaptive immunity have not been clarified. To investigate the impact of PON1 on the immune system, we generated PON1-knockout (PON1−/−) rats using the CRISPR/Cas9 system. The thymus was smaller in PON1−/− rats than that in wild-type (PON1+/+) rats. Furthermore, analysis of thymocyte development revealed diminished total T cell numbers and a decrease in CD4+, CD8+ and double-positive T cells in peripheral blood and thymus from PON1−/− rats. This may be due to a block in the transition of T cells from the double-negative to the double-positive stage. We also showed that the activation of p38 MAPK phosphorylation contributed to the increased apoptosis and defective T cell development in PON−/− rats. Therefore, our results indicate that PON1 functions as a novel regulator of T cell development.
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DOI：
10.1101/sqb.1989.054.01.018
发表时间：
1989-01-01
期刊：
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY
影响因子：
--
作者：
LOH, DY;SHA, WC;RUSSELL, JH
通讯作者：
RUSSELL, JH
影响因子：
5.1
作者：
Furlong CE;Marsillach J;Jarvik GP;Costa LG
通讯作者：
Costa LG
影响因子：
3.5
作者：
Mackness M;Mackness B
通讯作者：
Mackness B
影响因子：
3.3
作者：
Rosenblat, M.;Elias, A.;Aviram, M.
通讯作者：
Aviram, M.
影响因子：
4.4
作者：
Yamashita, Junji;Iwamura, Chiaki;Nakayama, Toshinori
通讯作者：
Nakayama, Toshinori