Paiatto Lisiery N, Silva Fernanda G D, Bier Julia, Brochetto-Braga Márcia R, Yamada Áureo T, Tamashiro Wirla M S C, Simioni Patricia U
Department of Genetics, Evolution and Bioagents, Institute of Biology, State University of Campinas, UNICAMP, Campinas, São Paulo, Brazil.
Institute of Biosciences, Universidade Estadual Paulista, UNESP, Rio Claro, São Paulo, Brazil.
PLoS One. 2017 Jan 18;12(1):e0170205. doi: 10.1371/journal.pone.0170205. eCollection 2017.
Literature data have shown that the consumption of dietary proteins may cause modulatory effects on the host immune system, process denominated oral tolerance by bystander suppression. It has been shown that the bystander suppression induced by dietary proteins can improve inflammatory diseases such as experimental arthritis. Here, we evaluated the effects of oral tolerance induced by ingestion of ovalbumin (OVA) on TNBS-induced colitis in mice, an experimental model for human Crohn's disease.
Colitis was induced in BALB/c mice by instilling a single dose of TNBS (100 mg/kg) in ethanol into the colon. Tolerized mice received OVA (4mg/mL) dissolved in the drinking water for seven consecutive days, prior to or concomitantly with the intrarectal instillation. Control groups received protein-free water and ethanol by intrarectal route. We observed that either the prior or concomitant induction of oral tolerance were able to reduce the severity of colitis as noted by recovery of body weight gain, improvement of clinical signs and reduction of histological abnormalities. The in vitro proliferation of spleen cells from tolerant colitic mice was lower than that of control mice, the same as the frequencies of CD4+ T cells secreting IL-17 and IFN-γ. The frequencies of regulatory T cells and T cells secreting IL-10 have increased significantly in mice orally treated with OVA. The levels of inflammatory cytokines (IL-17A, TNF-α, IL-6 and IFN-γ) were lower in supernatants of cells from tolerant colitic mice, whereas IL-10 levels were higher.
Our data show that the modulation of immune response induced by oral tolerance reduces the severity of experimental colitis. Such modulation may be partially attributed to the increase of Treg cells and reduction of pro-inflammatory cytokines in peripheral lymphoid organs of tolerant mice by bystander suppression.
文献数据表明，膳食蛋白质的摄入可能会对宿主免疫系统产生调节作用，这一过程被称为旁观者抑制引起的口服耐受。研究表明，膳食蛋白质诱导的旁观者抑制可以改善炎症性疾病，如实验性关节炎。在此，我们评估了摄入卵清蛋白（OVA）诱导的口服耐受对小鼠三硝基苯磺酸（TNBS）诱导的结肠炎的影响，这是一种人类克罗恩病的实验模型。
通过向BALB/c小鼠结肠内注入单剂量溶于乙醇的TNBS（100mg/kg）诱导结肠炎。耐受小鼠在直肠内注入TNBS之前或同时，连续7天饮用溶解有OVA（4mg/mL）的水。对照组通过直肠途径接受无蛋白水和乙醇。我们观察到，无论是预先还是同时诱导口服耐受，都能够减轻结肠炎的严重程度，表现为体重增加恢复、临床症状改善以及组织学异常减少。耐受的结肠炎小鼠脾细胞的体外增殖低于对照小鼠，分泌白细胞介素-17（IL-17）和干扰素-γ（IFN-γ）的CD4+T细胞频率也相同。用OVA口服处理的小鼠中，调节性T细胞和分泌IL-10的T细胞频率显著增加。耐受的结肠炎小鼠细胞上清液中炎症细胞因子（IL-17A、肿瘤坏死因子-α（TNF-α）、IL-6和IFN-γ）水平较低，而IL-10水平较高。
我们的数据表明，口服耐受诱导的免疫反应调节可减轻实验性结肠炎的严重程度。这种调节可能部分归因于旁观者抑制使耐受小鼠外周淋巴器官中调节性T细胞增加以及促炎细胞因子减少。
