8.Yamashita-Kanemaru Y, Oh-oka K, Abe F, Shibuya K, Shibuya A. Suppression of Th1 and Th17 proinflammatory cytokines and upregulation of Foxp3 expression by a humanized anti-DNAM-1 monoclonal antibody
8.Yamashita-Kanemaru Y, Oh-oka K, Abe F, Shibuya K, Shibuya A. Suppression of Th1 and Th17 proinflammatory cytokines and upregulation of Foxp3 expression by a humanized anti-DNAM-1 monoclonal antibody
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8.Yamashita-Kanemaru Y、Oh-oka K、Abe F、Shibuya K、Shibuya A。人源化抗 DNAM-1 单克隆抗体抑制 Th1 和 Th17 促炎细胞因子并上调 Foxp3 表达
DOI：
10.1089/mab.2020.0042
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发表时间：
2021
影响因子：
--
通讯作者：
Shibuya A.
中科院分区：
文献类型：
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作者：
Yamashita-Kanemaru Y;Oh-oka K;Abe F;Shibuya K;Shibuya A.
DNaM-1是一种活化的免疫受体，表达在造血细胞上，包括CD4+和CD8+T细胞、自然杀伤细胞和血小板。由于dNaM-1在人类和小鼠模型中参与了各种炎症性疾病和癌症的发病机制，因此它是这些疾病的免疫治疗的潜在靶点。在这项研究中，我们制备了人源化的中和抗人dNaM-1单抗，命名为TNAX101a，它含有人IgG1的Fc部分，以减少Fc介导的效应功能。我们发现TNAX101a有效地干扰了dNaM-1与其配体CD155的结合，并显示出独特的功能；它减少了抗CD3抗体刺激或同种异体抗原刺激的T细胞产生的炎性细胞因子，如干扰素-γ、肿瘤坏死因子α、白介素6、IL-17A和IL-17F，并增加了抗CD3刺激的调节性T细胞(Treg)的FOXP3表达。TNAX101a的这种双重功能可能通过下调效应T细胞功能和上调Treg细胞功能来治疗T细胞介导的炎症性疾病。
DNAM-1 is an activating immunoreceptor expressed on hematopoietic cells, including both CD4+and CD8+T cells, natural killer cells, and platelets. Since DNAM-1 is involved in the pathogenesis of various inflammatory diseases and cancers in humans as well as mouse models, it is a potential target for immunotherapy for these diseases. In this study, we generated a humanized neutralizing antihuman DNAM-1 monoclonal antibody (mAb), named TNAX101A, which contains an engineered Fc portion of human IgG1 to reduce Fc-mediated effector functions. We show that TNAX101A efficiently interfered the binding of DNAM-1 to its ligand CD155 and showed unique functions; it decreased production of the inflammatory cytokines such as interferon-gamma, tumor necrosis factor alpha, interleukin (IL)-6, IL-17A, and IL-17F by anti-CD3 antibody-stimulated or alloantigen-stimulated T cells and increased FOXP3 expression in anti-CD3-stimulated regulatory T (Treg) cells. These dual functions of TNAX101A may be advantageous for the treatment of T cell-mediated inflammatory diseases through both downregulation of effector T cell function and upregulation of Treg cell function.