Division of Trauma Surgery, Emergency Surgery & Surgical Critical, Tongji Trauma Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Emergency and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Cell Death Dis. 2024 Aug 21;15(8):606. doi: 10.1038/s41419-024-06992-0.
Lymphocyte decline, particularly the depletion of NK cells, is a prominent feature of immunosuppression following severe tissue injury, heightening the susceptibility of severe trauma patients to life-threatening infections. Previous research indicates that the reduction in the number of NK cells is closely associated with the process of cell death. Nonetheless, the precise mechanism of NK cell death remains unknown. Here, we discovered that following severe traumatic injury, NK cells undergo several cell death pathways, dominated by apoptosis and pyroptosis with coexistence of necrotic cell death, immunogenic cell death, ferroptosis, and autophagy. These NK cells with different paradigms of death have diverse cytokine expression profiles and diverse interactions with other immune cells. Further exploration revealed that hypoxia was strongly associated with this diverse paradigm of NK cell death. Detailed investigation of paradigms of cell death may help to enhance comprehension of lymphopenia post-severe trauma, to develop new strategy in preventing immunosuppression, and then to improve outcome for severe trauma population.
淋巴细胞减少,特别是 NK 细胞耗竭,是严重组织损伤后免疫抑制的一个显著特征,使严重创伤患者更容易受到危及生命的感染。先前的研究表明,NK 细胞数量的减少与细胞死亡过程密切相关。然而,NK 细胞死亡的确切机制尚不清楚。在这里,我们发现严重创伤后,NK 细胞经历了几种细胞死亡途径,以凋亡和焦亡为主,同时存在坏死性细胞死亡、免疫原性细胞死亡、铁死亡和自噬。这些具有不同死亡范式的 NK 细胞具有不同的细胞因子表达谱,并与其他免疫细胞有不同的相互作用。进一步的研究表明,缺氧与 NK 细胞的这种多种死亡范式密切相关。对细胞死亡范式的详细研究可能有助于提高对严重创伤后淋巴细胞减少的认识,制定预防免疫抑制的新策略,从而改善严重创伤患者的预后。