Unexpected role for the immunoproteasome subunit LMP2 in antiviral humoral and innate immune responses.
Unexpected role for the immunoproteasome subunit LMP2 in antiviral humoral and innate immune responses.
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DOI：
10.4049/jimmunol.0903003
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发表时间：
2010-04-15
期刊：
影响因子：
--
通讯作者：
Yewdell JW
中科院分区：
文献类型：
--
作者：
Hensley SE;Zanker D;Dolan BP;David A;Hickman HD;Embry AC;Skon CN;Grebe KM;Griffin TA;Chen W;Bennink JR;Yewdell JW
蛋白酶体是多亚基蛋白酶，其起始由MHC I类分子呈递的许多Ag的降解。脊椎动物表达三种催化蛋白酶体亚基中的每一种的替代形式：标准亚基和免疫亚基，其由APC组成性表达，并通过暴露于细胞因子而在其他细胞类型中诱导。含有标准亚基和免疫亚基的混合蛋白酶体的组装以组织特异性方式调节。在这项研究中，我们报告说，LMP 2 −/−小鼠免疫细胞中混合蛋白酶体的存在损害了有助于产生抗病毒抗体应答的多种成分，包括脾B细胞数量、过继转移的B细胞的存活和功能、Th细胞功能以及树突状细胞分泌IL-6、TNF-α、IL-1β和I型IFN。这些缺陷不是由于整体蛋白质降解受损所致，而是与NF-κB活性改变相关。这些发现表明免疫蛋白酶体在免疫细胞功能中的重要作用超出了它们对Ag加工的贡献。
Proteasomes are multisubunit proteases that initiate degradation of many Ags presented by MHC class I molecules. Vertebrates express alternate forms of each of the three catalytic proteasome subunits: standard subunits, and immunosubunits, which are constitutively expressed by APCs and are induced in other cell types by exposure to cytokines. The assembly of mixed proteasomes containing standard subunits and immunosubunits is regulated in a tissue specific manner. In this study, we report that the presence of mixed proteasomes in immune cells in LMP2−/− mice compromises multiple components that contribute to the generation of antiviral Ab responses, including splenic B cell numbers, survival and function of adoptively transferred B cells, Th cell function, and dendritic cell secretion of IL-6, TNF-α, IL-1β, and type I IFNs. These defects did not result from compromised overall protein degradation, rather they were associated with altered NF-κB activity. These findings demonstrate an important role for immunoproteasomes in immune cell function beyond their contribution to Ag processing.
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影响因子：
56.9
作者：
LOWE, J;STOCK, D;HUBER, R
通讯作者：
HUBER, R
影响因子：
64.8
作者：
FAN, CM;MANIATIS, T
通讯作者：
MANIATIS, T
免疫蛋白酶体塑造抗病毒CD8（+）T细胞在T细胞库水平和病毒抗原的表现下的免疫主导层次结构。
影响因子：
15.3
作者：
Chen, W;Norbury, C C;Cho, Y;Yewdell, J W;Bennink, J R
通讯作者：
Bennink, J R
影响因子：
32.4
作者：
Jego, G;Palucka, AK;Banchereau, J
通讯作者：
Banchereau, J
DOI：
10.1084/jem.187.1.97
发表时间：
1998-01-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Griffin TA;Nandi D;Cruz M;Fehling HJ;Kaer LV;Monaco JJ;Colbert RA
通讯作者：
Colbert RA