NKG2D ligand RAE1ε induces generation and enhances the inhibitor function of myeloid-derived suppressor cells in mice.
NKG2D ligand RAE1ε induces generation and enhances the inhibitor function of myeloid-derived suppressor cells in mice.
复制标题
NKG2D 配体 Rae1μ 诱导小鼠骨髓源性抑制细胞的生成并增强其抑制剂功能
DOI：
10.1111/jcmm.13124
复制
发表时间：
2017-09
影响因子：
5.3
通讯作者：
Tian F
中科院分区：
文献类型：
--
作者：
Qian L;Liu Y;Wang S;Gong W;Jia X;Liu L;Ye F;Ding J;Xu Y;Fu Y;Tian F
肿瘤细胞表面NKG 2D配体的表达激活自然杀伤（NK）细胞和CD 8 + T细胞，在抗肿瘤免疫中至关重要。某些类型的肿瘤已经形成了抑制NKG 2D介导的免疫细胞活化的机制，例如肿瘤源性可溶性NKG 2D配体或肿瘤产生的持续性NKG 2D配体下调NK细胞和CD 8 + T细胞上NKG 2D的表达。在这里，我们报告了肿瘤细胞表面NKG 2D配体RAE 1 ε通过NKG 2D在体外和体内诱导CD 11b +Gr-1+髓源性抑制细胞（MDSC）。RAE 1 ε诱导的MDSC显示出对IL-10和IL-10酶的强烈诱导，并且这些MDSC通过抑制抗原-非特异性CD 8 + T细胞增殖显示出更大的抑制活性。一致地，在过继转移后，RAE 1 ε诱导的MDSC以IL-10和β-淀粉酶依赖性方式显著促进CT 26肿瘤生长。RAE 1 ε在体内使细胞因子平衡向Th 2而不是Th 1移动。此外，RAE 1 ε增强CT 26衍生MDSC的抑制功能，并在体外通过NKG 2D促进CT 26衍生MDSC产生IL-4而不是IFN-γ。我们的研究证明了NKG 2D配体+肿瘤细胞通过促进MDSC的增殖和抑制功能而逃避免疫监视的新机制。
Expression of surface NKG2D ligands on tumour cells, which activates nature killer (NK) cells and CD8+ T cells, is crucial in antitumour immunity. Some types of tumours have evolved mechanisms to suppress NKG2D‐mediated immune cell activation, such as tumour‐derived soluble NKG2D ligands or sustained NKG2D ligands produced by tumours down‐regulate the expression of NKG2D on NK cells and CD8+ T cells. Here, we report that surface NKG2D ligand RAE1ε on tumour cells induces CD11b+Gr‐1+ myeloid‐derived suppressor cell (MDSC) via NKG2D in vitro and in vivo. MDSCs induced by RAE1ε display a robust induction of IL‐10 and arginase, and these MDSCs show greater suppressive activity by inhibiting antigen‐non‐specific CD8+ T‐cell proliferation. Consistently, upon adoptive transfer, MDSCs induced by RAE1ε significantly promote CT26 tumour growth in IL‐10‐ and arginase‐dependent manners. RAE1ε moves cytokine balance towards Th2 but not Th1 in vivo. Furthermore, RAE1ε enhances inhibitory function of CT26‐derived MDSCs and promotes IL‐4 rather than IFN‐γ production from CT26‐derived MDSCs through NKG2D in vitro. Our study has demonstrated a novel mechanism for NKG2D ligand+ tumour cells escaping from immunosurveillance by facilitating the proliferation and the inhibitory function of MDSCs.
登录
查看更多内容
癌症扩增的骨髓源性抑制细胞通过膜结合 TGF-β1 诱导 NK 细胞无反应。
影响因子：
4.4
作者：
Li, Hequan;Han, Yanmei;Cao, Xuetao
通讯作者：
Cao, Xuetao
影响因子：
2.9
作者：
Qian, Li;Zhang, Yue;Tian, Fang
通讯作者：
Tian, Fang
影响因子：
32.4
作者：
Sade-Feldman, Moshe;Kanterman, Julia;Baniyash, Michal
通讯作者：
Baniyash, Michal
影响因子：
11.2
作者：
Sinha, Pratima;Clements, Virginia K.;Ostrand-Rosenberg, Suzanne
通讯作者：
Ostrand-Rosenberg, Suzanne
影响因子：
20.3
作者：
Agaugue, Sophie;Carosella, Edgardo D.;Rouas-Freiss, Nathalie
通讯作者：
Rouas-Freiss, Nathalie