Usp18 promotes conventional CD11b+ dendritic cell development.
Usp18 promotes conventional CD11b+ dendritic cell development.
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DOI：
10.4049/jimmunol.1101609
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发表时间：
2012-05-15
期刊：
影响因子：
--
通讯作者：
Zhang DE
中科院分区：
文献类型：
--
作者：
Cong XL;Lo MC;Reuter BA;Yan M;Fan JB;Zhang DE
树突状细胞（Dendritic cells，DC）是连接先天性免疫和适应性免疫的关键细胞。因此，了解调控DC分化的分子因素至关重要。Usp 18是干扰素（IFN）诱导的泛素特异性蛋白酶（USP）家族成员，其将泛素样修饰物ISG 15从靶蛋白解缀合，并竞争性抑制IFN-α/β诱导的JAK/STAT活化。本研究表明，Usp 18 −/−小鼠脾脏中常规CD 11b + DC的频率显著降低，而常规CD 8 + DC和浆细胞样DC的频率保持正常。此外，Usp 18 −/−骨髓（BM）细胞在GM-CSF补充培养中产生DC的效率较低，表明整个DC分化途径存在根本缺陷。Usp 18 −/− BM细胞通过野生型或去缀合失活的Usp 18的外源性表达而被拯救，而叠加IFN-α/β受体敲除使体内DC群体恢复正常，清楚地表明所观察到的缺陷仅仅是由于Usp 18对IFN信号传导的影响。最后，Usp 18 −/− BM-DCs表达高水平的SOCS 1/SOCS 3，这是已知的GM-CSF信号传导抑制剂，为表型提供了机制解释。总之，我们已经确定了一个新的作用，Usp 18在调节传统的CD 11b + DC的发展，通过其抑制作用对I型干扰素信号。
Dendritic cells (DCs) represent the key cells linking innate and adaptive immune responses. It is critical to understand the molecular factors regulating DC differentiation. Usp18 is an interferon (IFN)-inducible member of the ubiquitin-specific protease (USP) family, which deconjugates ubiquitin-like modifier ISG15 from target proteins, and competitively inhibits IFN-α/β-induced JAK/STAT activation. This studydemonstrates that the frequency of conventional CD11b+ DCs in the spleen of Usp18−/− mice was significantly reduced, while the frequencies of conventional CD8+ DCs and plasmacytoid DCs remained normal. In addition, Usp18−/− bone marrow (BM) cells generate DCs less efficiently in GM-CSF-supplemented culture, demonstrating a fundamental defect throughout the DC differentiation pathway. Usp18−/− BM cells were rescued by exogenous expression of either wild type, or deconjugation-inactive, Usp18, while superimposition of an IFN-α/β receptor knockout returned in vivo DC populations to normal, clearly showing that the defect seen is due solely to Usp18’s effect on IFN signaling. Finally, Usp18−/− BM-DCs expressed high levels of SOCS1/SOCS3, known inhibitors of GM-CSF signaling, providing a mechanistic explanation for the phenotype. In conclusion, we have identified a novel role of Usp18 in modulating conventional CD11b+ DC development via its inhibitory effect on Type I interferon signaling.
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影响因子：
4.4
作者：
Kim, KI;Malakhova, OA;Zhang, DE
通讯作者：
Zhang, DE
影响因子：
4.8
作者：
Malakhova, O;Malakhov, M;Zhang, DE
通讯作者：
Zhang, DE
DOI：
10.1126/science.1170540
发表时间：
2009-04-17
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Liu K;Victora GD;Schwickert TA;Guermonprez P;Meredith MM;Yao K;Chu FF;Randolph GJ;Rudensky AY;Nussenzweig M
通讯作者：
Nussenzweig M
影响因子：
56.9
作者：
Takaoka, A;Mitani, Y;Taniguchi, T
通讯作者：
Taniguchi, T
DOI：
10.1073/pnas.0307336101
发表时间：
2004-02-24
影响因子：
11.1
作者：
Honda, K;Mizutani, T;Taniguchi, T
通讯作者：
Taniguchi, T