Molecular and Histological Profiling Reveals an Innate-Shaped Immune Microenvironment in Solitary Juvenile Polyps.
Molecular and Histological Profiling Reveals an Innate-Shaped Immune Microenvironment in Solitary Juvenile Polyps.
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DOI：
10.14309/ctg.0000000000000361
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发表时间：
2021-06-01
影响因子：
3.6
通讯作者：
Sokollik C
中科院分区：
文献类型：
--
作者：
Zysset D;Montani M;Spalinger J;Schibli S;Zlobec I;Mueller C;Sokollik C
孤立性幼年性息肉（JP）的特点是良性的疾病过程，复发率低，但目前有肠道炎症的迹象。为了更好地了解潜在的发病机制，我们针对不同的免疫机制进行了组织学和分子评价。研究了儿童JP患者（n = 12）、初治炎症性肠病（IBD; [n = 41]）作为炎症对照和非IBD对照（n = 14）。对于浸润免疫细胞的比较分析，组装下一代活检组织微阵列，进行免疫染色和评分。使用定制的免疫学小组进行靶向转录谱分析。在JP中，观察到中性粒细胞和嗜酸性粒细胞的主要蓄积。RNA表达谱显示，在JP中CXCL 8、CXCL 5和CCL 11转录物水平增加，表明中性粒细胞和嗜酸性粒细胞的募集增强。此外，促炎细胞因子IL 1b和炎症放大受体TREM 1的信使RNA水平在JP中更高，而与IBD相比，我们在JP中没有发现功能极化T细胞反应的迹象。JP患者和初治IBD患者在活动性疾病期间有不同的细胞浸润。JP中大量存在嗜酸性粒细胞支持中性粒细胞蓄积，这是钙卫蛋白释放升高的原因。然而，有趣的是，我们无法在JP中识别功能极化的T细胞应答，这表明在JP炎症急性发作期间，没有建立有效的适应性免疫记忆。这可能解释了JP的低复发率。
Solitary juvenile polyps (JP) are characterized by a benign disease course with low recurrence rate but present with signs of intestinal inflammation. To better understand the underlying pathogenesis, we performed histological and molecular evaluation targeting distinct immune mechanisms. Pediatric patients with JP (n = 12), with treatment-naïve inflammatory bowel disease (IBD; [n = 41]) as inflammatory control, and non-IBD controls (n = 14) were investigated. For a comparative analysis of infiltrating immune cells, a next-generation tissue microarray of biopsies was assembled, immunostained, and scored. Targeted transcriptional profiling was performed using a customized immunology panel. In JP, a predominant accumulation of neutrophils and eosinophils was observed. RNA expression profiles revealed increased levels of CXCL8, CXCL5, and CCL11 transcripts in JP, indicating an enhanced recruitment of neutrophils and eosinophils. Moreover, messenger RNA levels of the proinflammatory cytokine IL1b and the inflammation-amplifying receptor TREM1 were higher in JP, whereas we could not find signs of a functionally polarized Tcell response in JP when compared with IBD. Patients with JP and patients with treatment-naïve IBD have distinct cell infiltrates during active disease. The ample presence of eosinophils in JP supports neutrophil accumulation, which is responsible for the elevated release of calprotectin. Intriguingly, however, we were not able to identify a functionally polarized T-cell response in JP, which indicates that during the acute onset of inflammation in JP, a potent adaptive immune memory is not established. This may explain the low reoccurrence rate of JP.
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嗜酸性粒细胞介导的小肠稳态和IgA产生中的IL-1β。
影响因子：
8
作者：
通讯作者：
--
影响因子：
29.4
作者：
Howell KJ;Kraiczy J;Nayak KM;Gasparetto M;Ross A;Lee C;Mak TN;Koo BK;Kumar N;Lawley T;Sinha A;Rosenstiel P;Heuschkel R;Stegle O;Zilbauer M
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Zilbauer M
影响因子：
6.1
作者：
Persson, T;Monsef, N;Egesten, A
通讯作者：
Egesten, A
影响因子：
4.9
作者：
Iboshi, Yoichiro;Nakamura, Kazuhiko;Takayanagi, Ryoichi
通讯作者：
Takayanagi, Ryoichi
用福尔马林固定，石蜡包裹的材料的RNA表达分析。
影响因子：
2.7
作者：
Oberli A;Popovici V;Delorenzi M;Baltzer A;Antonov J;Matthey S;Aebi S;Altermatt HJ;Jaggi R
通讯作者：
Jaggi R