CD95/Fas, Non-Apoptotic Signaling Pathways, and Kinases.
CD95/Fas, Non-Apoptotic Signaling Pathways, and Kinases.
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DOI：
10.3389/fimmu.2017.01216
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发表时间：
2017
影响因子：
7.3
通讯作者：
Legembre P
中科院分区：
文献类型：
--
作者：
Le Gallo M;Poissonnier A;Blanco P;Legembre P
在炎症性疾病或癌症期间形成的新血管内壁的内皮细胞充当着允许或阻止进入肿瘤或发炎器官的大门。最近的数据表明，狼疮患者的癌症组织和发炎组织中的这些内皮细胞过度表达CD95L，其生物学作用是一个有争议的话题。受体 CD95（也称为 Fas 或凋亡抗原 1）属于肿瘤坏死因子 (TNF) 受体超家族。其同源配体 CD95L 与免疫稳态和免疫监视有关。由于该受体或其配体的突变会导致系统性红斑狼疮 (SLE) 和癌症等自身免疫性疾病，因此 CD95 和 CD95L 最初被认为通过细胞凋亡信号通路在免疫稳态和肿瘤消除中发挥作用。然而，最近的数据表明，CD95 也会引发非凋亡信号，促进炎症，并导致癌变；因此，在疾病发病过程中很难将其凋亡作用与非凋亡作用区分开来。 CD95L 被金属蛋白酶切割，因此以两种不同的形式存在：跨膜形式和可溶性配体 (s-CD95L)。我们最近观察到，可溶性配体在三阴性乳腺癌或 SLE 患者的血清中过度表达，它通过激活非凋亡信号通路并促进受损器官中某些 T 细胞亚群的转移扩散或积累，从而导致疾病严重程度。在这里，我们讨论 CD95 通过诱导主要非凋亡信号通路来调节免疫功能的作用。
Endothelial cells lining new blood vessels that develop during inflammatory disorders or cancers act as doors that either allow or block access to the tumor or inflamed organ. Recent data show that these endothelial cells in cancer tissues and inflamed tissues of lupus patients overexpress CD95L, the biological role of which is a subject of debate. The receptor CD95 (also named Fas or apoptosis antigen 1) belongs to the tumor necrosis factor (TNF) receptor superfamily. Its cognate ligand, CD95L, is implicated in immune homeostasis and immune surveillance. Because mutations of this receptor or its ligand lead to autoimmune disorders such as systemic lupus erythematosus (SLE) and cancers, CD95 and CD95L were initially thought to play a role in immune homeostasis and tumor elimination via apoptotic signaling pathways. However, recent data reveal that CD95 also evokes non-apoptotic signals, promotes inflammation, and contributes to carcinogenesis; therefore, it is difficult to dissect its apoptotic effects from its non-apoptotic effects during pathogenesis of disease. CD95L is cleaved by metalloproteases and so exists in two different forms: a transmembrane form and a soluble ligand (s-CD95L). We recently observed that the soluble ligand is overexpressed in serum from patients with triple-negative breast cancer or SLE, in whom it contributes to disease severity by activating non-apoptotic signaling pathways and promoting either metastatic dissemination or accumulation of certain T cell subsets in damaged organs. Here, we discuss the roles of CD95 in modulating immune functions via induction of mainly non-apoptotic signaling pathways.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
32.4
作者：
Basu R;O'Quinn DB;Silberger DJ;Schoeb TR;Fouser L;Ouyang W;Hatton RD;Weaver CT
通讯作者：
Weaver CT
DOI：
10.1073/pnas.94.8.3943
发表时间：
1997-04-15
影响因子：
11.1
作者：
Allison, J;Georgiou, HM;Vaux, DL
通讯作者：
Vaux, DL
影响因子：
56.9
作者：
Chen, JJ;Sun, YN;Nabel, GJ
通讯作者：
Nabel, GJ