Mucosal Invariant T cells are Diminished in Very Early-Onset Inflammatory Bowel Disease.
Mucosal Invariant T cells are Diminished in Very Early-Onset Inflammatory Bowel Disease.
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DOI：
10.1097/mpg.0000000000003189
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发表时间：
2021-10-01
影响因子：
2.9
通讯作者：
Kelsen J
中科院分区：
文献类型：
--
作者：
Dou Y;Maurer K;Conrad M;Patel T;Shraim R;Sullivan KE;Kelsen J
非常早发性炎症性肠病发生于6岁以下的儿童，这是肠道微生物群免疫发育和成熟的关键时期。非常规淋巴细胞，这里定义为粘膜相关的不变T细胞和先天淋巴细胞，需要微生物产物来发育或扩张，这些方面可能在非常早发的炎症性肠病中发生改变。我们的目的是使用多参数流式细胞术来定义对照组和患者中的常规白细胞和非常规淋巴细胞群，以验证其频率在与显著生态失调相关的慢性炎症状态下会发生改变的假设。多参数流式细胞术在105名对照队列中使用，以确定年龄效应，以前没有在人类中对这些细胞类型进行全面检查。使用学生t检验确定263例年龄匹配的非常早发性炎症性肠病患者与105例对照患者之间的差异。在抽样时，受试者被分为两个年龄组，以控制与年龄相关的免疫组成变化。与对照组相比，VEO-IBD患者的中间单核细胞持续减少。黏膜相关的不变性T细胞在长期疾病患者中显著降低。其水平还不到同龄对照组的一半。先天性淋巴样细胞2型群在最年轻的患者中扩大。粘膜相关的不变T细胞在出现炎症性肠病数年后减少。这种早期肠道炎症的持久影响可能有长期的后果。减少粘膜相关的不变性T细胞可能影响宿主对肠道感染的防御。
Very early-onset inflammatory bowel disease arises in children less than six years old, a critical time for immunologic development and maturation of the intestinal microbiome. Non-conventional lymphocytes, defined here as mucosal-associated invariant T cells and innate lymphocytes, require microbial products for either development or expansion, aspects that could be altered in very early-onset inflammatory bowel disease. Our objective was to define conventional leukocyte and non-conventional lymphocyte populations in controls and patients using multiparameter flow cytometry to test the hypothesis that their frequencies would be altered in a chronic inflammatory state associated with significant dysbiosis. Multiparameter flow cytometry was used in a control cohort of 105 subjects to define age-effects, not previously comprehensively examined for these cell types in humans. Differences were defined between 263 unique age-matched patients with very early-onset inflammatory bowel disease and 105 controls using Student’s t test. Subjects were divided into two age groups at the time of sampling to control for age-related changes in immune composition. Intermediate monocytes were consistently decreased in patients with VEO-IBD compared to controls. Mucosal-associated invariant T cells were significantly lower in patients with long-standing disease. Levels were less than half of those seen in the age-matched control cohort. The innate lymphoid cells type 2 population was expanded in the youngest patients. Mucosal-associated invariant T cells are diminished years after presentation with inflammatory bowel disease. This durable effect of early life intestinal inflammation may have long term consequences. Diminished mucosal-associated invariant T cells could impact host defense of intestinal infections.