SAP 通过与 CD28 相互作用来抑制 T 淋巴细胞中的 PD-1 信号通路。
SAP interacts with CD28 to inhibit PD-1 signaling in T lymphocytes.
机构信息
Department of Medicine, NYU School of Medicine, New York, NY 10016, USA.
Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA.
出版信息
Clin Immunol. 2020 Aug;217:108485. doi: 10.1016/j.clim.2020.108485. Epub 2020 Jun 3.
T cell co-stimulation is important for the maintenance of immunologic tolerance. Co-inhibitory receptors including programmed cell death-1 (PD-1) confer peripheral tolerance to prevent autoimmunity. SAP (SH2D1A) is an adaptor molecule that is important in T cell signaling and has been shown to interact with signaling lymphocytic activation molecule (SLAM) family receptors also in the context of self-tolerance. We recently reported that SAP interferes with PD-1 function. In the current study, we investigated the levels of SAP and PD-1 in patients with rheumatoid arthritis (RA) to further understand what role they play in disease activity. We observed increased SAP levels in lymphocytes of RA patients and found that PD-1 levels correlated positively with RA disease activity. Additionally, we found that SAP interacts with CD28 to inhibit T cell signaling in vitro. This work demonstrates a putative molecular mechanism for SAP mediated PD-1 inhibition.
T 细胞共刺激对于维持免疫耐受很重要。共抑制受体，包括程序性细胞死亡-1（PD-1），赋予外周耐受以防止自身免疫。SAP（SH2D1A）是一种衔接分子，在 T 细胞信号转导中很重要，并已被证明在自身耐受的情况下与信号淋巴细胞激活分子（SLAM）家族受体相互作用。我们最近报道 SAP 干扰 PD-1 功能。在本研究中，我们调查了类风湿关节炎（RA）患者的 SAP 和 PD-1 水平，以进一步了解它们在疾病活动中的作用。我们观察到 RA 患者淋巴细胞中的 SAP 水平升高，并发现 PD-1 水平与 RA 疾病活动呈正相关。此外，我们发现 SAP 与 CD28 相互作用，在体外抑制 T 细胞信号转导。这项工作证明了 SAP 介导的 PD-1 抑制的一种假定分子机制。
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