RGMb is a novel binding partner for PD-L2 and its engagement with PD-L2 promotes respiratory tolerance.
RGMb is a novel binding partner for PD-L2 and its engagement with PD-L2 promotes respiratory tolerance.
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DOI：
10.1084/jem.20130790
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发表时间：
2014-05-05
期刊：
影响因子：
--
通讯作者：
Freeman GJ
中科院分区：
文献类型：
--
作者：
Xiao Y;Yu S;Zhu B;Bedoret D;Bu X;Francisco LM;Hua P;Duke-Cohan JS;Umetsu DT;Sharpe AH;DeKruyff RH;Freeman GJ
树突状细胞上的抑制性分子PD-L2和肺巨噬细胞上的排斥性导向分子B（RGMB）之间的相互作用是建立呼吸耐受所必需的。我们报道了程序性死亡配体2（PD-L2），一种已知的PD-1配体，也与排斥性导向分子B（RGMB）结合，RGMb最初在神经系统中被鉴定为骨形态发生蛋白（BMP）的共受体。PD-L2和BMP-2/4结合RGMb上的不同位点。正常静息肺间质巨噬细胞和肺泡上皮细胞表达高水平的RGMb mRNA，而肺树突状细胞表达PD-L2。阻断RGMb-PD-L2相互作用通过干扰呼吸耐受所需的初始T细胞扩增而显著损害呼吸耐受的发展。PD-L2缺陷小鼠的实验表明，PD-L2在非T细胞上的表达对于呼吸耐受至关重要，但在T细胞上的表达不是必需的。由于PD-L2与抑制抗肿瘤免疫的PD-1和调节呼吸免疫的RGMb结合，因此靶向PD-L2通路对哮喘、癌症和其他免疫介导的疾病具有治疗潜力。了解这一途径可以提供有关如何在癌症免疫治疗中最佳调节PD-1途径，同时最大限度地减少不良事件的见解。
Interaction between the inhibitory molecule PD-L2 on dendritic cells and repulsive guidance molecule b (RGMb) on lung macrophages is required to establish respiratory tolerance. We report that programmed death ligand 2 (PD-L2), a known ligand of PD-1, also binds to repulsive guidance molecule b (RGMb), which was originally identified in the nervous system as a co-receptor for bone morphogenetic proteins (BMPs). PD-L2 and BMP-2/4 bind to distinct sites on RGMb. Normal resting lung interstitial macrophages and alveolar epithelial cells express high levels of RGMb mRNA, whereas lung dendritic cells express PD-L2. Blockade of the RGMb–PD-L2 interaction markedly impaired the development of respiratory tolerance by interfering with the initial T cell expansion required for respiratory tolerance. Experiments with PD-L2–deficient mice showed that PD-L2 expression on non–T cells was critical for respiratory tolerance, but expression on T cells was not required. Because PD-L2 binds to both PD-1, which inhibits antitumor immunity, and to RGMb, which regulates respiratory immunity, targeting the PD-L2 pathway has therapeutic potential for asthma, cancer, and other immune-mediated disorders. Understanding this pathway may provide insights into how to optimally modulate the PD-1 pathway in cancer immunotherapy while minimizing adverse events.
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影响因子：
13
作者：
Corradini, Elena;Babitt, Jodie L.;Lin, Herbert Y.
通讯作者：
Lin, Herbert Y.
DOI：
10.1084/jem.194.6.769
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
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通讯作者：
Nussenzweig MC
影响因子：
4
作者：
Li, Jin;Ye, Lin;Jiang, Wen G.
通讯作者：
Jiang, Wen G.
影响因子：
30.5
作者：
Latchman, Y;Wood, CR;Freeman, GJ
通讯作者：
Freeman, GJ
影响因子：
15.9
作者：
Bedoret, Denis;Wallemacq, Hugues;Bureau, Fabrice
通讯作者：
Bureau, Fabrice