Single cell analysis via mass cytometry of spontaneous intestinal perforation reveals alterations in small intestinal innate and adaptive mucosal immunity.

Single cell analysis via mass cytometry of spontaneous intestinal perforation reveals alterations in small intestinal innate and adaptive mucosal immunity.
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DOI:
10.3389/fimmu.2023.995558
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发表时间:
2023
影响因子:
7.3
通讯作者:
Konnikova L
Konnikova L
中科院分区:
医学2区
文献类型:
--
作者:
Olaloye O;Eke C;Jolteus A;Konnikova L

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自发性肠穿孔(SIP)是一种人们知之甚少的严重早产儿胃肠道并发症。妊娠 28 周之前出生的极早产儿在出生后第一周会出现回肠末端局部穿孔,治疗方法包括手术和停止肠内喂养。关于粘膜免疫功能障碍对疾病发病机制的影响知之甚少。我们对 SIP 患者(胎龄 (GA) 24 – 27 周,n=8)的小肠粘膜进行了质谱流式细胞仪飞行时间 (CyTOF) 分析,与因非 SIP 情况接受手术的患者(新生儿(GA > 36 周,n=5)和选择性终止妊娠的胎儿肠(GA 18-21 周,n=4)进行比较。用 PMA/离子霉素刺激 T 细胞后也进行了 CyTOF 分析。我们注意到 SIP 中先天性和适应性粘膜免疫的变化,其中 ckit+ 中性粒细胞增多,效应记忆 T 细胞减少,其特征是刺激后 CCR6 和 CXCR3 表达减少,干扰素 γ 表达增加。
Spontaneous intestinal perforation (SIP) is a poorly understood severe gastrointestinal complications of prematurity which is poorly understood. Extremely premature infants born prior to 28 weeks’ gestation develop a localized perforation of the terminal ileum during the first week of life and therapy involves surgery and cessation of enteral feeds. Little is known regardj g the impact of mucosal immune dysfunction on disease pathogenesis. We performed mass cytometry time of flight (CyTOF) of small intestinal mucosa of patients with SIP (Gestational age (GA) 24 – 27 weeks, n=8) compared to patients who had surgery for non-SIP conditions (neonatal (GA >36 weeks, n=5 ) and fetal intestine from elective terminations (GA 18-21 weeks, n=4). CyTOF analysis after stimulation of T cells with PMA/Ionomycin was also performed. We noted changes in innate and adaptive mucosal immunity in SIP. SIP mucosa had an expansion of ckit+ neutrophils, an influx of naïve CD4 and CD8 T cells and a reduction of effector memory T cells. SIP T cells were characterized by reduced CCR6 and CXCR3 expression and increased interferon gamma expression after stimulation. These findings suggest that previously unrecognized immune dysregulation is associated with SIP and should be explored in future studies.
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