Regulation of T cell proliferation by JMJD6 and PDGF-BB during chronic hepatitis B infection.
Regulation of T cell proliferation by JMJD6 and PDGF-BB during chronic hepatitis B infection.
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DOI：
10.1038/srep06359
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发表时间：
2014-09-15
影响因子：
4.6
通讯作者：
He YW
中科院分区：
文献类型：
--
作者：
Chen CF;Feng X;Liao HY;Jin WJ;Zhang J;Wang Y;Gong LL;Liu JJ;Yuan XH;Zhao BB;Zhang D;Chen GF;Wan Y;Guo J;Yan HP;He YW
慢性乙型肝炎病毒（HBV）感染时T细胞功能衰竭可能导致病毒清除失败；然而，潜在的分子机制在很大程度上仍然未知。在这里，我们证明了病毒结构域蛋白6 （JMJD6）是慢性HBV感染期间T细胞增殖的潜在调节剂。慢性乙型肝炎（CHB）患者的T淋巴细胞中JMJD6的表达降低，并且这种JMJD6表达的降低与T细胞增殖受损有关。此外，在原代人T细胞中沉默JMJD6的表达会损害T细胞的增殖。我们发现JMJD6通过抑制CDKN3 mRNA的表达来促进T细胞增殖。此外，我们已经确定血小板衍生生长因子- bb （PDGF-BB）是JMJD6表达的调节因子。PDGF-BB下调JMJD6的表达，抑制人原代T细胞的增殖。重要的是，CHB患者淋巴细胞中JMJD6和PDGF-BB的表达水平与肝损伤程度和慢性HBV感染治疗结果相关。我们的研究结果表明，PDGF-BB和JMJD6在慢性HBV感染期间调节T细胞功能，并可能为慢性乙型肝炎患者的治疗策略提供见解。
T cell functional exhaustion during chronic hepatitis B virus (HBV) infection may contribute to the failed viral clearance; however, the underlying molecular mechanisms remain largely unknown. Here we demonstrate that jumonji domain-containing protein 6 (JMJD6) is a potential regulator of T cell proliferation during chronic HBV infection. The expression of JMJD6 was reduced in T lymphocytes in chronic hepatitis B (CHB) patients, and this reduction in JMJD6 expression was associated with impaired T cell proliferation. Moreover, silencing JMJD6 expression in primary human T cells impaired T cell proliferation. We found that JMJD6 promotes T cell proliferation by suppressing the mRNA expression of CDKN3. Furthermore, we have identified platelet derived growth factor-BB (PDGF-BB) as a regulator of JMJD6 expression. PDGF-BB downregulates JMJD6 expression and inhibits the proliferation of human primary T cells. Importantly, the expression levels of JMJD6 and PDGF-BB in lymphocytes from CHB patients were correlated with the degree of liver damage and the outcome of chronic HBV infection treatment. Our results demonstrate that PDGF-BB and JMJD6 regulate T cell function during chronic HBV infection and may provide insights for the treatment strategies for CHB patients.
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影响因子：
64.5
作者：
GYURIS, J;GOLEMIS, E;BRENT, R
通讯作者：
BRENT, R
影响因子：
15.3
作者：
Das, Abhishek;Hoare, Matthew;Davies, Nathan;Lopes, A. Ross;Dunn, Claire;Kennedy, Patrick T. F.;Alexander, Graeme;Finney, Helene;Lawson, Alistair;Plunkett, Fiona J.;Bertoletti, Antonio;Akbar, Arne N.;Maini, Mala K.
通讯作者：
Maini, Mala K.
DOI：
10.1073/pnas.91.5.1731
发表时间：
1994-03-01
影响因子：
11.1
作者：
HANNON, GJ;CASSO, D;BEACH, D
通讯作者：
BEACH, D
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DOI：
10.1083/jcb.200309126
发表时间：
2004-03-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Swaminathan S;Kiendl F;Körner R;Lupetti R;Hengst L;Melchior F
通讯作者：
Melchior F
影响因子：
64.5
作者：
Liu W;Ma Q;Wong K;Li W;Ohgi K;Zhang J;Aggarwal A;Rosenfeld MG
通讯作者：
Rosenfeld MG