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克罗恩病和溃疡性结肠炎中肌间神经丛免疫细胞浸润及神经递质表达

Myenteric Plexus Immune Cell Infiltrations and Neurotransmitter Expression in Crohn's Disease and Ulcerative Colitis.

作者信息

Wiese Jakob J, Manna Subhakankha, Kühl Anja A, Fascì Alberto, Elezkurtaj Sefer, Sonnenberg Elena, Bubeck Marvin, Atreya Raja, Becker Christoph, Weixler Benjamin, Siegmund Britta, Patankar Jay V, Prüß Magdalena S, Schumann Michael

机构信息

Medizinische Klinik m. S. Gastroenterologie, Infektiologie und Rheumatologie, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.

Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, iPATH.Berlin, Berlin, Germany.

出版信息

J Crohns Colitis. 2024 Jan 27;18(1):121-133. doi: 10.1093/ecco-jcc/jjad122.

Abstract

BACKGROUND AND AIMS

Pain is a cardinal symptom in inflammatory bowel disease [IBD]. An important structure in the transduction of pain signalling is the myenteric plexus [MP]. Nevertheless, IBD-associated infiltration of the MP by immune cells lacks in-depth characterisation. Herein, we decipher intra- and periganglionic immune cell infiltrations in Crohn´s disease [CD] and ulcerative colitis [UC] and provide a comparison with murine models of colitis.

METHODS

Full wall specimens of surgical colon resections served to examine immune cell populations by either conventional immuno-histochemistry or immunofluorescence followed by either bright field or confocal microscopy. Results were compared with equivalent examinations in various murine models of intestinal inflammation.

RESULTS

Whereas the MP morphology was not significantly altered in IBD, we identified intraganglionic IBD-specific B cell- and monocyte-dominant cell infiltrations in CD. In contrast, UC-MPs were infiltrated by CD8+ T cells and revealed a higher extent of ganglionic cell apoptosis. With regard to the murine models of intestinal inflammation, the chronic dextran sulphate sodium [DSS]-induced colitis model reflected CD [and to a lesser extent UC] best, as it also showed increased monocytic infiltration as well as a modest B cell and CD8+ T cell infiltration.

CONCLUSIONS

In CD, MPs were infiltrated by B cells and monocytes. In UC, mostly CD8+ cytotoxic T cells were found. The chronic DSS-induced colitis in the mouse model reflected best the MP-immune cell infiltrations representative for IBD.

摘要

背景与目的

疼痛是炎症性肠病(IBD)的主要症状。痛觉信号转导中的一个重要结构是肌间神经丛(MP)。然而,IBD相关的免疫细胞对MP的浸润缺乏深入的特征描述。在此,我们解析克罗恩病(CD)和溃疡性结肠炎(UC)中神经节内和神经节周围的免疫细胞浸润情况,并与结肠炎小鼠模型进行比较。

方法

手术切除的结肠全壁标本用于通过常规免疫组织化学或免疫荧光检查免疫细胞群体,随后进行明场或共聚焦显微镜观察。将结果与各种肠道炎症小鼠模型的等效检查进行比较。

结果

虽然IBD中MP的形态没有明显改变,但我们在CD中发现了神经节内IBD特异性的以B细胞和单核细胞为主的细胞浸润。相比之下,UC-MP被CD8 + T细胞浸润,并且神经节细胞凋亡程度更高。关于肠道炎症小鼠模型,慢性葡聚糖硫酸钠(DSS)诱导的结肠炎模型最能反映CD(在较小程度上反映UC),因为它也显示出单核细胞浸润增加以及适度的B细胞和CD8 + T细胞浸润。

结论

在CD中,MP被B细胞和单核细胞浸润。在UC中,主要发现CD8 + 细胞毒性T细胞。小鼠模型中的慢性DSS诱导的结肠炎最能反映IBD代表性的MP免疫细胞浸润情况。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc6a/10821712/b69db8d7f607/jjad122_fig1.jpg

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