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CD147 调节免疫突触的形成和功能。

CD147 regulates the formation and function of immune synapses.

机构信息

Department of Clinical Immunology, Xijing Hospital, and Department of Cell Biology of National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, China.

Department of Clinical Immunology, Xijing Hospital, and Department of Cell Biology of National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, China; Department of Immunology, School of Basic Medicine, Xian Medical University, Xi'an, China.

出版信息

Cell Immunol. 2024 Jul-Aug;401-402:104845. doi: 10.1016/j.cellimm.2024.104845. Epub 2024 Jun 19.

DOI:10.1016/j.cellimm.2024.104845
PMID:38909549
Abstract

CD147 is a T cell activation-associated molecule which is closely involved in the formation of the immune synapse (IS). However, the precise role of CD147 in T cell activation and IS formation remains unclear. In the present study, we demonstrated that CD147 translocated to the IS upon T cell activation and was primarily distributed in the peripheral super molecular cluster (p-SMAC). The knock down of CD147 expression in T cells, but not in B cells, impaired IS formation. CD147 participated in IS formation between T cells and different types of antigen-presenting cells (APCs), including macrophages and dendritic cells. Ligation of CD147 with its monoclonal antibody (mAb) HAb18 effectively inhibited T cell activation and IL-2 secretion. CD98, a critical molecule interacting with CD147, was distributed in IS in a CD147-dependent way. Phosphorylation levels of T cell receptor (TCR) related molecules, like ZAP-70, ERK, and cJun, were down-regulated by CD147 ligation, which is crucial for the interaction of CD147 and TCR signaling transduction. CD147 is indispensable for the formation of immune synapses and plays an important role in the regulation of its function.

摘要

CD147 是一种 T 细胞激活相关分子,它与免疫突触(IS)的形成密切相关。然而,CD147 在 T 细胞激活和 IS 形成中的精确作用尚不清楚。在本研究中,我们证明了 CD147 在 T 细胞激活时向 IS 易位,并主要分布在外周超分子簇(p-SMAC)中。在 T 细胞而非 B 细胞中敲低 CD147 的表达会损害 IS 的形成。CD147 参与了 T 细胞与不同类型的抗原呈递细胞(APC)之间的 IS 形成,包括巨噬细胞和树突状细胞。用其单克隆抗体(mAb)HAb18 交联 CD147 可有效抑制 T 细胞激活和 IL-2 分泌。CD98 是与 CD147 相互作用的关键分子,以依赖 CD147 的方式分布在 IS 中。T 细胞受体(TCR)相关分子如 ZAP-70、ERK 和 cJun 的磷酸化水平被 CD147 交联下调,这对于 CD147 和 TCR 信号转导的相互作用至关重要。CD147 对于免疫突触的形成是不可或缺的,并且在调节其功能方面发挥着重要作用。

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