摘要
目的 探究溃疡性结肠炎(UC)患者外周血黏膜相关恒定T(MAIT)细胞的亚群及表型改变,为临床诊断及治疗提供新的思路.方法 前瞻性收集2023年1月至2024年5月首都医科大学附属北京友谊医院消化科确诊的30例UC患者作为研究组,并以同时期体检中心收集的同年龄段30名健康志愿者作为对照组.通过使用MR1-tetramer标记MAIT细胞,比较研究组及对照组外周血MAIT细胞的比例及炎症因子[γ-干扰素(IFN-γ)、白细胞介素(IL)-17A、Perforin、Granzyme B、肿瘤坏死因子α(TNF-α)]的表达情况,并分析CX3CR1+MAIT细胞的表型改变及其与疾病进展的相关性.结果 研究组外周血MAIT细胞在CD3+T细胞中的比例与对照组比较,差异无统计学意义(P＞0.05).研究组 MAIT 细胞中 Granzyme B、Perforin、IFN-γ 及 TNF-α 阳性群体的比例分别为(39.75±19.55)％、(16.95±11.18)％、(36.97±14.20)％、(46.13±13.88)％,均显著高于对照组[(24.57±14.88)％、(10.02±6.69)％、(25.22±17.08)％、(35.77±22.77)％],差异均有统计学意义(P＜0.05);两组MAIT细胞IL-17A的表达水平比较,差异无统计学意义(P＞0.05).研究组外周血MAIT细胞中CX3C趋化因子受体1(CX3CR1)+群体的比例为(81.67±12.29)％,显著高于对照组[(57.88±19.73)％],而 KLRG1+群体的比例为(49.74±12.96)％,明显低于对照组[(60.22±14.54)％],差异均有统计学意义(P＜0.05).研究组与对照组CX3CR1+MAIT细胞的KLRG1表达水平比较,差异无统计学意义(P＞0.05).研究组外周血CX3CR1+MAIT细胞中Granzyme B、IFN-γ及TNF-α阳性群体的比例分别为(44.95±19.28)％、(37.49±13.66)％、(44.84±11.97)％,均显著高于对照组[(33.87±13.71)％、(24.79±13.88)％、(34.31±17.21)％],差异均有统计学意义(P＜0.05);两组CX3CR1+MAIT细胞Perforin、IL-17 A的表达水平比较,差异均无统计学意义(P＞0.05).CX3CR1+MAIT细胞Granzyme B、Perforin的表达水平均显著高于CX3CR1-群体,差异均有统计学意义(P＜0.05);而CX3CR1+MAIT细胞IFN-γ及TNF-α的表达水平与CX3CR1-群体比较,差异均无统计学意义(P＞0.05).UC患者外周血中CX3CR1+MAIT细胞的比例与简化临床结肠炎活动指数呈显著正相关(P＜0.05).结论 在发生UC后,患者外周血MAIT细胞发生显著活化,其中高表达CX3CR1的杀伤性群体显著增多.相关性分析则进一步提示外周血CX3CR1+MAIT细胞可能在肠炎进程中发挥重要作用.
Abstract
Objective Investigate the alterations of peripheral blood mucosal-associated invariant T(MAIT)cells in patients with ul-cerative colitis(UC),and provide new ideas for clinical diagnosis and treatment.Methods Thirty UC patients diagnosed in the Department of Gastroenterology,Beijing Friendship Hospital,Capital Medical University from January 2023 to May 2024 were prospectively collected as the study group,while 30 healthy volunteers of the same age were collected as the control group.MAIT cells were labeled with MR1-tetramer.The propor-tion of MAIT cells in peripheral blood and their expression of inflammatory cytokines[γ-interferon(IFN-γ),interleukin(IL)-17 A,Perfor-in,Granzyme B,tumor necrosis factor α(TNF-α)]were compared between the study group and control group.The alterations of CX3CR1+MAIT cells and their correlation with disease progression were also analyzed.Results There was no significant difference in the proportion of MAIT cells in CD3+T populations between the study group and control group(P＞0.05).The percentages of Granzyme B,Perforin,IFN-γ and TNF-α positive populations in MAIT cells of the study group were(39.75±19.55)％,(16.95±11.18)％,(36.97±14.20)％and(46.13±13.88)％,respectively,which were significantly higher than those of the control group[(24.57±14.88)％,(10.02±6.69)％,(25.22±17.08)％,(35.77±22.77)％],and the differences were statistically significant(P＜0.05),while the expression level of IL-17A in MAIT cells between the two groups was comparable(P＞0.05).The proportion of CX3C chemokine receptor 1(CX3CR1)+populations in peripheral blood MAIT cells of the study group was(81.67±12.29)％,which was significantly higher than that of the control group[(57.88±19.73)％],while the proportion of KLRG1+MAIT population was(49.74±12.96)％,which was significantly lower than that of the control group[(60.22±14.54)％],the level of KLRG1 expression in CX3CR1+MAIT cells between the two groups was comparable(P＞0.05).The percentages of Granzyme B,IFN-γ and TNF-α positive populations in peripheral blood CX3CR1+MAIT cells of study group were(44.95±19.28)％,(37.49±13.66)％,(44.84±11.97)％,respectively,which were significantly higher than those of the control group[(33.87±13.71)％,(24.79±13.88)％and(34.31±17.21)％],and the differences were statistically significant(P＜0.05).The expression levels of Perforin and IL-17A in CX3CR1+MAIT cells between the two groups were also comparable(P＞0.05).The levels of Granzyme B and Perforinn expres-sion in CX3CR1+MAIT cells were significantly higher than CX3CR1-counterparts,and the differences were statistically significant(P＜0.05).The expression levels of IFN-γ and TNF-α were comparable between CX3CR1+MAIT cells and CX3CR1-counterparts(P＞0.05).The pro-portion of CX3CR1+MAIT cells in peripheral blood of UC patients was positively correlated with the simplified clinical colitis activity index(P＜0.05).Conclusion During the ulcerative colitis,MAIT cells in peripheral blood are significantly activated,and a unique CX3CR1+cytotoxic cluster increases significantly among them.The correlation analysis further reveals that peripheral blood CX3CR1+MAIT cells may play an impor-tant role in the process of enteritis.
NETL
NSTL
万方数据