Sun Xingfeng, Nan Ke, Zhong Ziwen, Liu Zhiqiang, Miao Changhong
Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Department of Anesthesiology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200090, China.
Acta Biochim Biophys Sin (Shanghai). 2025 May 30;57(8):1325-1337. doi: 10.3724/abbs.2025087.
Persistent inflammation-immunosuppression and catabolism syndrome (PICS) is a severe condition that may follow sepsis and is characterized by ongoing inflammation and immune suppression, diminishing quality of life and potentially causing death. The role of megakaryocytes (MKs) in PICS, despite their association with thrombopoiesis, is not well understood. In this study, we use single-cell RNA sequencing to profile MKs in peripheral blood mononuclear cell samples obtained from 11 patients, including six with PICS, five with sepsis, and five healthy controls, to determine the diversity and molecular signatures of the MKs. Five subgroups of MKs are identified (MK1-MK5), and their proportions vary across the groups. MK1 and MK2 are predominant in PICS. Gene Ontology analysis shows that genes related to antigen processing and presentation and IL-17 signaling are enriched in MK1, whereas genes associated with platelet degranulation and neutrophil activation are enriched in MK2. Moreover, the expression level of CCL5 is markedly increased in MKs. Ligand-receptor analysis reveals dynamic interactions among MKs and T cells, B cells, natural killer cells, monocytes, and macrophages, suggesting a broad role of MKs in immune homeostasis. In PICS model mice, MKs regulate systemic inflammation by reducing the levels of the proinflammatory cytokines TNF-α and IL-17A and promoting lung tissue repair. Our findings establish MKs as essential components of the immune system in PICS and provide new insights into their potential as therapeutic targets for post-sepsis immune dysfunction.
持续性炎症-免疫抑制和分解代谢综合征（PICS）是一种可能在脓毒症后出现的严重病症，其特征是炎症持续存在和免疫抑制，生活质量下降并可能导致死亡。尽管巨核细胞（MKs）与血小板生成有关，但其在PICS中的作用尚不清楚。在本研究中，我们使用单细胞RNA测序对从11名患者获得的外周血单核细胞样本中的MKs进行分析，其中包括6名患有PICS的患者、5名患有脓毒症的患者和5名健康对照，以确定MKs的多样性和分子特征。鉴定出MKs的五个亚组（MK1-MK5），它们在各组中的比例有所不同。MK1和MK2在PICS中占主导地位。基因本体分析表明，与抗原加工和呈递以及IL-17信号相关的基因在MK1中富集，而与血小板脱颗粒和中性粒细胞活化相关的基因在MK2中富集。此外，MKs中CCL5的表达水平显著增加。配体-受体分析揭示了MKs与T细胞、B细胞、自然杀伤细胞、单核细胞和巨噬细胞之间的动态相互作用，表明MKs在免疫稳态中具有广泛作用。在PICS模型小鼠中，MKs通过降低促炎细胞因子TNF-α和IL-17A的水平并促进肺组织修复来调节全身炎症。我们的研究结果确定MKs是PICS中免疫系统的重要组成部分，并为其作为脓毒症后免疫功能障碍治疗靶点的潜力提供了新的见解。
