Modulation of Immune Cell Functions by the E3 Ligase Cbl-b.
Modulation of Immune Cell Functions by the E3 Ligase Cbl-b.
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通过E3连接酶CBL-B调节免疫细胞功能。
DOI：
10.3389/fonc.2015.00058
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发表时间：
2015
影响因子：
4.7
通讯作者：
Sopper S
中科院分区：
文献类型：
--
作者：
Lutz-Nicoladoni C;Wolf D;Sopper S
维持免疫耐受是免疫系统的一个重要标志。到目前为止，已经描述了平衡免疫细胞激活和抑制输入所必需的几个信号检查点，其中E3连接酶Cbl-b似乎是一个核心角色。Cbl-b在所有白细胞亚群中表达，并调节T细胞、NK细胞、B细胞和不同类型的髓细胞中的几种信号通路。在大多数情况下，Cbl-b通过抗原或模式识别受体和共刺激分子负性调节激活信号。与此功能一致，cblb缺陷免疫细胞表现出较低的激活阈值，cblb敲除小鼠自发产生自身免疫，并且对实验性自身免疫高度敏感。有趣的是，遗传关联研究也将人类的cblb多态性与自身免疫联系起来。反之亦然，缺陷细胞激活电位的增加使它们更有能力对抗恶性肿瘤或感染。因此，一些报道表明，cblb敲除小鼠排斥肿瘤，主要依赖于细胞毒性T和NK细胞。因此，靶向Cbl-b可能是一种有趣的增强抗癌免疫的策略。在本文中，我们综述了在不同细胞类型中关于细胞再生酶b的分子功能的研究结果，并阐述了细胞再生酶b作为免疫调节治疗靶点的潜力。
Maintenance of immunological tolerance is a critical hallmark of the immune system. Several signaling checkpoints necessary to balance activating and inhibitory input to immune cells have been described so far, among which the E3 ligase Cbl-b appears to be a central player. Cbl-b is expressed in all leukocyte subsets and regulates several signaling pathways in T cells, NK cells, B cells, and different types of myeloid cells. In most cases, Cbl-b negatively regulates activation signals through antigen or pattern recognition receptors and co-stimulatory molecules. In line with this function, cblb-deficient immune cells display lower activation thresholds and cblb knockout mice spontaneously develop autoimmunity and are highly susceptible to experimental autoimmunity. Interestingly, genetic association studies link CBLB-polymorphisms with autoimmunity also in humans. Vice versa, the increased activation potential of cblb-deficient cells renders them more potent to fight against malignancies or infections. Accordingly, several reports have shown that cblb knockout mice reject tumors, which mainly depends on cytotoxic T and NK cells. Thus, targeting Cbl-b may be an interesting strategy to enhance anti-cancer immunity. In this review, we summarize the findings on the molecular function of Cbl-b in different cell types and illustrate the potential of Cbl-b as target for immunomodulatory therapies.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
7.7
作者：
Abe T;Hirasaka K;Kagawa S;Kohno S;Ochi A;Utsunomiya K;Sakai A;Ohno A;Teshima-Kondo S;Okumura Y;Oarada M;Maekawa Y;Terao J;Mills EM;Nikawa T
通讯作者：
Nikawa T
影响因子：
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作者：
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通讯作者：
Bracken MB
影响因子：
15.9
作者：
Chiang, Jeffrey Y.;Jang, Ihn Kyung;Gu, Hua
通讯作者：
Gu, Hua
影响因子：
2.5
作者：
Banica, Leontina M.;Besliu, Alina N.;Matache, Cristiana
通讯作者：
Matache, Cristiana