慢性鼻窦炎伴鼻息肉患者外周血与息肉组织CD8+T细胞免疫功能和组织蛋白学分析及与RASAL3关系研究OA
Analysis of CD8+T Cell Immune Function and Tissue Proteomics in Peripheral Blood and Polyp Tissue of Patients with Chronic Rhinosinusitis with Nasal Polyps and Their Relationship with RASAL3
目的 探讨慢性鼻窦炎伴鼻息肉(CRSwNP)患者外周血与息肉组织CD8+T细胞浸润和免疫功能抑制的影响因素及其与Ras激活蛋白样3(RASAL3)表达相关性,明确CRSwNP的免疫治疗机制.方法 选取2023年4月～2024年3月云南省中医医院耳鼻喉科收治的20例CRSwNP 患者为研究对象,同时收集患者外周血和鼻息肉组织.同期20例健康体检人群作为对照组.采用流式细胞术检测外周血和鼻息肉组织T淋巴细胞亚群、CD8+T细胞毒性功能及T细胞CD39和PD-1的表达.20例研究对象中随机选取5例CRSwNP鼻息肉和4例鼻中隔偏曲患者的钩突或鼻甲黏膜组织进行组织蛋白学研究.结果 与健康人群外周血组相比,CRSwNP外周血组CD8+T细胞颗粒酶B和穿孔素表达升高,差异具有统计学意义(t=3.229、2.133,均P<0.05).与自身外周血组相比,鼻息肉组T淋巴细胞以CD8+T细胞升高为主(t=6.024,P<0.001),颗粒酶B和穿孔素表达下降(u=11.000、38.000),CD39和PD-1表达上升(u=59.500、46.000),差异具有统计学意义(均P<0.001).组织蛋白学研究共鉴定到6 275个蛋白,与鼻中隔偏曲组相比,CRSwNP组显著变化的蛋白有470个,其中表达量上调蛋白181个,RASAL3在CRSwNP组显著上调,差异具有统计学意义(P<0.05),并负向调控T细胞受体信号通路.结论CRSwNP鼻息肉中,T淋巴细胞亚群分布以CD8+T细胞升高为主,随着CD39和PD-1表达上调,CD8+T细胞分泌颗粒酶B和穿孔素能力下降,处于免疫抑制状态.息肉组织中高表达的RASAL3参与CD8+T细胞的浸润及功能抑制的调控.
Objective This study investigated factors influencing CD8+T cell infiltration and immune function suppression in pe-ripheral blood and polyp tissues of patients with chronic rhinosinusitis with nasal polyps(CRSwNP).The correlation between these factors and Ras protein activator like 3(RASAL3)expression was examined to clarify the immunotherapeutic mechanisms of CRSwNP.Methods Twenty CRSwNP patients treated in the department of otolaryngology at Yunnan Provincial Hospital of Traditional Chinese Medicine from April 2023 to March 2024 were enrolled.Peripheral blood and nasal polyp tissues were col-lected.Twenty healthy individuals undergoing physical examinations served as the control group.Flow cytometry was used to analyze T lymphocyte subsets,CD8+T cell cytotoxic function,and expression of CD39 and PD-1 in T cells from both peripheral blood and polyp tissues.Tissue proteomic analysis was performed on polyp tissues from five randomly selected CRSwNP pa-tients and mucosal tissues from the uncinate process or turbinate of four patients with deviated nasal septum.Results Compared with the healthy control group,the CRSwNP peripheral blood group showed increased expression of granzyme B and perforin in CD8+T cells.Statistical significance was observed(t=3.229,2.133,both P<0.05).Compared with their own peripheral blood,the nasal polyp group exhibited a predominant increase in CD8+T cells(t=6.024,P<0.001).Expression of granzyme B and perforin decreased(u=11.000,38.000),while expression of CD39 and PD-1 increased(u=59.500,46.000),the differences were statistical-ly significant(all P<0.001).Tissue proteomic analysis identified 6 275 proteins.Compared with the deviated nasal septum group,470 proteins showed significant changes in the CRSwNP group,with 181 proteins upregulated.RASAL3 expression was significantly upregulated in the CRSwNP group(P<0.05).RASAL3 was found to negatively regulate the T cell receptor signaling pathway.Conclusions In CRSwNP nasal polyps,T lymphocyte subset distribution was characterized by a predominant increase in CD8+T cells.Elevated expression of CD39 and PD-1 correlated with reduced secretion of granzyme B and perforin by CD8+T cells,indicating an immunosuppressive state.Highly expressed RASAL3 in polyp tissues was involved in regulating CD8+T cell infiltration and functional suppression.
刘骥;李亚波;黄春江;谭凌翔;刘益州
云南中医药大学第一附属医院 云南省中医医院 耳鼻喉科,昆明 650021云南中医药大学第一附属医院 云南省中医医院 检验科,昆明 650021云南中医药大学第一附属医院 云南省中医医院 耳鼻喉科,昆明 650021云南中医药大学第一附属医院 云南省中医医院 耳鼻喉科,昆明 650021北京中医药大学中医学院,北京 102488
医药卫生
慢性鼻窦炎伴鼻息肉CD8+T细胞组织蛋白学Ras激活蛋白样3流式细胞术
chronic rhinosinusitis with nasal polypsCD8+T cellsproteomicsRas GTPase-activating protein-like 3flow cytometry
《现代检验医学杂志》 2026 (5)
52-57,70,7
云南省科技厅中医联合专项面上项目(202301AZ070001-080)云南中医药大学校院联合基金项目(XYLH202201).
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