Immunobiology of TNFSF15 and TNFRSF25
Immunobiology of TNFSF15 and TNFRSF25
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DOI：
10.1007/s12026-013-8465-0
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发表时间：
2013-12-01
影响因子：
4.4
通讯作者：
Podack, Eckhard R.
中科院分区：
文献类型：
--
作者：
Schreiber, Taylor H.;Podack, Eckhard R.
TNFRSF 25是一种未充分研究的广泛作用的T细胞共刺激分子，与TNFR 1具有高度同源性，然而，该受体在T细胞免疫生物学中的总体作用尚不清楚。TNFRSF 25与其单配体TNFSF 15（TL 1A）的连接导致原代T细胞中TNFR相关因子2和TNFR相关死亡结构域的募集，同时下游激活NF κ B以及PI 3 K/Akt轴。这些信号传导途径依赖于T细胞受体和白细胞介素-2受体的协调接合，并导致CD 4 + FoxP 3+调节性T细胞（Treg）的组成性增殖，这是由于紧张性暴露于自身抗原的结果。CD 4+或CD 8+常规T细胞克隆的同时活化取决于同源外源抗原的可用性。在这里，我们提供了一个审查的文献和我们的工作对这种受体，并提出TL 1A信号转导TNFRSF 25在T细胞的整体功能是提供同时共刺激的外来抗原特异性效应T细胞和预先存在的调节性T细胞，以集中克隆性的效应免疫病原体衍生的抗原，并减少对自身或内源性微生物抗原的旁观者炎症的风险。
TNFRSF25 is an understudied broad-acting T cell costimulator with high homology to TNFR1, however, the overall role of this receptor in T cell immunobiology is unclear. Ligation of TNFRSF25 by its monogamous ligand, TNFSF15 (TL1A), leads to recruitment of TNFR-associated factor 2 and TNFR-associated death domain in primary T cells with downstream activation of both NF kappa B as well as the PI3K/Akt axis. These signaling pathways are dependent upon coordinated engagement of the T cell receptor and interleukin-2 receptor and leads to the constitutive proliferation of CD4+FoxP3+ regulatory T cells (Treg) as a result of tonic exposure to self-antigen. Concurrent activation of CD4+ or CD8+ conventional T cell clones is dependent upon the availability of cognate foreign antigen. Here, we provide a review of both the literature and our work on this receptor and propose that the overall function of TL1A signaling to TNFRSF25 in T cells is to provide simultaneous costimulation of foreign-antigen-specific effector T cells and pre-existing Treg in order to focus the clonality of effector immunity to pathogen-derived antigens and reduce the risk of bystander inflammation toward self- or endogenous microbial antigens.