Biological variability of human intraepithelial lymphocytes throughout the human gastrointestinal tract in health and coeliac disease

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation Pub Date : 2024-08-29 DOI:10.1111/eci.14304

Aida Fiz-López, Ángel De Prado, Elisa Arribas-Rodríguez, Francisco Javier García-Alonso, Sandra Izquierdo, Álvaro Martín-Muñoz, José A. Garrote, Eduardo Arranz, Jesús Barrio, Luis Fernández-Salazar, David Bernardo

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Abstract

Background

Intraepithelial lymphocytes are the first line of defence of the human intestinal immune system. Besides, their composition is altered on patients with coeliac disease (CD), so they are considered as biomarkers with utility on their diagnose and/or monitoring. Our aim is to address their variability through the human gastrointestinal tract in health and characterized them in further depth in the coeliac duodenum.

Methods

Intraepithelial lymphocytes were isolated from human gastric, duodenal, ileal and colonic biopsies, then stained with specific antibodies and acquired by flow cytometry.

Results

Our results confirmed that the profile of Intraepithelial lymphocytes change through the length of the human gastrointestinal tract. Besides and given the central role that Interleukin-15 (IL-15) elicits on CD pathogenesis; we also assessed the expression of its receptor revealing that there was virtually no functional IL-15 receptor on duodenal Intraepithelial lymphocytes. Nevertheless and contrary to our expectations, the active IL-15 receptor was not increased either on Intraepithelial lymphocytes from CD patients.

Conclusions

IL-15 might require additional stimulus to activate intraepithelial lymphocytes. These findings may provide novel tools to aid on a CD diagnosis and/or monitoring, at the time that provide the bases to perform functional studies in order of getting a deeper insight in the specific function that Intraepithelial lymphocytes elicit on CD pathogenesis.

Abstract Image

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健康和乳糜泻患者整个胃肠道上皮内淋巴细胞的生物变异性。

背景：上皮内淋巴细胞是人体肠道免疫系统的第一道防线：上皮内淋巴细胞是人体肠道免疫系统的第一道防线。此外，上皮内淋巴细胞的组成在乳糜泻（CD）患者中会发生改变，因此它们被认为是诊断和/或监测乳糜泻的生物标志物。我们的目的是研究这些淋巴细胞在健康人胃肠道中的变化，并进一步深入研究它们在糜烂性十二指肠中的特征：方法：从人的胃、十二指肠、回肠和结肠活检组织中分离上皮内淋巴细胞，然后用特异性抗体染色并用流式细胞术检测：结果：我们的研究结果证实，上皮内淋巴细胞在人的胃肠道中的分布会发生变化。此外，鉴于白细胞介素-15（IL-15）在 CD 发病机制中的核心作用，我们还对其受体的表达进行了评估，结果显示十二指肠上皮内淋巴细胞几乎没有功能性 IL-15 受体。然而，与我们的预期相反，CD 患者上皮内淋巴细胞的活性 IL-15 受体也没有增加：IL-15可能需要额外的刺激才能激活上皮内淋巴细胞。这些发现可能为 CD 诊断和/或监测提供了新的辅助工具，同时也为进行功能研究提供了基础，以便更深入地了解上皮内淋巴细胞在 CD 发病机制中的特定功能。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Clinical Investigation 医学-医学：内科

CiteScore

9.50

自引率

3.60%

发文量

192

审稿时长

1 months

期刊介绍： EJCI considers any original contribution from the most sophisticated basic molecular sciences to applied clinical and translational research and evidence-based medicine across a broad range of subspecialties. The EJCI publishes reports of high-quality research that pertain to the genetic, molecular, cellular, or physiological basis of human biology and disease, as well as research that addresses prevalence, diagnosis, course, treatment, and prevention of disease. We are primarily interested in studies directly pertinent to humans, but submission of robust in vitro and animal work is also encouraged. Interdisciplinary work and research using innovative methods and combinations of laboratory, clinical, and epidemiological methodologies and techniques is of great interest to the journal. Several categories of manuscripts (for detailed description see below) are considered: editorials, original articles (also including randomized clinical trials, systematic reviews and meta-analyses), reviews (narrative reviews), opinion articles (including debates, perspectives and commentaries); and letters to the Editor.