Xia Tianqi, Han Fei, Wang Yaning, Xie Xinyue, Yuan Chenchen, Lu Guotao, Xiao Weiming, Tu Bo, Ren Hongbo, Gong Weijuan, Wang Yaodong
Pancreatic Center, Department of Gastroenterology, the Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225000, People's Republic of China.
Yangzhou Key Laboratory of Pancreatic Disease, the Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225000, People's Republic of China.
J Inflamm Res. 2025 Mar 13;18:3725-3739. doi: 10.2147/JIR.S507886. eCollection 2025.
The tetraspanin CD53 transmembrane protein is vital in immune cells like B cells and T cells, playing a crucial role in various inflammatory conditions. However, its involvement in neutrophils regarding inflammation remains uncertain. This study aims to examine the impact of CD53 on neutrophil extracellular traps (NETs) formation.
Phorbol 12-myristate 13-acetate (PMA) was utilized to establish an in vitro classical NETs model to investigate the influence of CD53 on NETs formation and its regulatory mechanisms. Subsequently, the link between CD53 and acute pancreatitis (AP), a model of aseptic inflammatory responses connected to NETs, was verified. Peripheral blood neutrophils from clinical AP patients were collected to explore the role of CD53 in AP, while an AP mouse model induced by caerulein was employed to confirm the impact of CD53 inhibition on AP mice pancreatic tissue.
Our study has shown that CD53 is significantly elevated in in vitro NETs models and neutrophils from AP patients. The expression of CD53 is closely related to the clinical prognosis of AP patients. At the same time, CD53 neutralizing antibody (Anti-CD53) can significantly inhibit the formation of NETs in vitro, inflammatory injury in AP mice and the formation of NETs in damaged tissues. Mechanistically, CD53 can modulate the PI3K/AKT pathway and promote the formation of NETs. Finally, targeted regulation of CD53 can effectively reduce inflammatory injury and NETs formation in damaged tissues of AP mice.
The results of this study mark the first confirmation that CD53 plays a crucial role in NETs formation. Targeting CD53 inhibition could potentially serve as a novel therapeutic approach for the treatment of AP.
四跨膜蛋白CD53跨膜蛋白在B细胞和T细胞等免疫细胞中至关重要，在各种炎症状态中发挥关键作用。然而，其在中性粒细胞炎症方面的作用仍不明确。本研究旨在探讨CD53对中性粒细胞胞外诱捕网（NETs）形成的影响。
利用佛波酯12 -肉豆蔻酸酯13 -乙酸酯（PMA）建立体外经典NETs模型，以研究CD53对NETs形成的影响及其调控机制。随后，验证了CD53与急性胰腺炎（AP）（一种与NETs相关的无菌性炎症反应模型）之间的联系。收集临床AP患者的外周血中性粒细胞以探讨CD53在AP中的作用，同时采用雨蛙肽诱导的AP小鼠模型来证实CD53抑制对AP小鼠胰腺组织的影响。
我们的研究表明，在体外NETs模型和AP患者的中性粒细胞中，CD53显著升高。CD53的表达与AP患者的临床预后密切相关。同时，CD53中和抗体（抗CD53）可显著抑制体外NETs的形成、AP小鼠的炎症损伤以及受损组织中NETs的形成。机制上，CD53可调节PI3K/AKT通路并促进NETs的形成。最后，对CD53的靶向调控可有效减轻AP小鼠受损组织中的炎症损伤和NETs形成。
本研究结果首次证实CD53在NETs形成中起关键作用。靶向抑制CD53可能成为治疗AP的一种新的治疗方法。
