Virally-induced upregulation of heparan sulfate on B cells via the action of type I IFN.
Virally-induced upregulation of heparan sulfate on B cells via the action of type I IFN.
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DOI：
10.4049/jimmunol.1003495
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发表时间：
2011-12-01
期刊：
影响因子：
--
通讯作者：
Coscoy L
中科院分区：
文献类型：
--
作者：
Jarousse N;Trujillo DL;Wilcox-Adelman S;Coscoy L
细胞表面硫酸乙酰肝素（HS）是许多细胞因子、趋化因子和生长因子的重要共受体。在这里，我们报告说，脾脏小鼠B细胞表达非常少的HS，并与γ疱疹病毒（MHV 68）或β疱疹病毒（MCMV）感染后，HS是迅速上调的表面B细胞。在I型IFN（IFN-I）受体缺陷的小鼠中未观察到HS上调。此外，用IFN-1诱导剂聚肌苷聚胞苷酸（poly I：C）处理野生型小鼠，触发了B细胞表面的HS表达。类似地，纯化的脾B细胞与IFN-1、TLR配体或B细胞受体刺激剂离体孵育导致HS表面表达的急剧增加。我们发现，IFN-Ⅰ诱导HS修饰的多配体蛋白聚糖4的表面表达增加，以及一个身份不明的HSPG。最后，IFN-1处理增加了B细胞对APRIL的反应性，APRIL是一种参与B细胞存活和T细胞非依赖性B细胞反应的细胞因子。从IFN-1处理的B细胞中酶促去除HS抑制APRIL信号传导。总之，我们的结果表明，在疱疹病毒感染小鼠后，由于IFN-Ⅰ的作用，HS在B细胞表面迅速上调，潜在地增加了B细胞对细胞因子的反应性。先天性免疫应答的刺激物在B细胞表面诱导HS表达可能在稳健免疫应答的发展中起关键作用。
Cell surface heparan sulfate (HS) is an important co-receptor for many cytokines, chemokines, and growth factors. Here we report that splenic murine B cells express very little HS, and that upon infection with either gammaherpesvirus (MHV68) or betaherpesvirus (MCMV), HS is rapidly upregulated at the surface of B cells. HS upregulation was not observed in mice deficient for the type-I IFN (IFN-I) receptor. Additionally, treatment of wild-type mice with the IFN-I inducer polyinosine polycytidylic acid (poly I:C) triggered HS expression at the B cell surface. Similarly, incubation of purified splenic B cells with IFN-I, TLR ligands, or B cell receptor stimulators ex vivo resulted in a drastic increase in HS surface expression. We found that IFN-I induced an increase in the surface expression of HS-modified syndecan 4 as well as that of an unidentified HSPG. Finally, IFN-I treatment increased B cell responsiveness to APRIL, a cytokine involved in B cell survival and T cell-independent B cell responses. Enzymatic removal of HS from IFN-I treated B cells inhibited APRIL signaling. Altogether, our results indicate that upon herpesvirus infection in mice, HS is rapidly upregulated at the surface of B cells due to the action of IFN-I, potentially increasing B cell responsiveness to cytokines. Induction of HS expression at the B cell surface by stimulators of the innate immune response is likely playing a key role in the development of a robust immune response.
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DOI：
10.1084/jem.20042393
发表时间：
2005-03-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dias S;Silva H Jr;Cumano A;Vieira P
通讯作者：
Vieira P
影响因子：
5.4
作者：
Jarousse, Nadine;Chandran, Bala;Coscoy, Laurent
通讯作者：
Coscoy, Laurent
影响因子：
5.4
作者：
Jones, KS;Petrow-Sadowski, C;Ruscetti, FW
通讯作者：
Ruscetti, FW
影响因子：
4.4
作者：
Chang, W. L. William;Coro, Elizabeth S.;Baumgarth, Nicole
通讯作者：
Baumgarth, Nicole
影响因子：
7.5
作者：
Lambaerts K;Wilcox-Adelman SA;Zimmermann P
通讯作者：
Zimmermann P