Institute of Applied Molecular Medicine, Hospitals Madrid (HM) Group, San Pablo-CEU University, Madrid, Spain.
Service of Gastroenterology, University Hospital San Agustin (HUSA), Aviles, Spain.
Front Immunol. 2021 Feb 25;12:623805. doi: 10.3389/fimmu.2021.623805. eCollection 2021.
Celiac disease (CD) is a chronic autoimmune disease characterized by an immune-triggered enteropathy upon gluten intake. The only current treatment available is lifelong Gluten Free Diet (GFD). Several extraintestinal manifestations have been described in CD, some affecting the oral mucosa. Thus, we hypothesized that oral mucosa could potentially be a target for novel biomarkers and an administration route for CD treatment. Six diagnosed and seven CD patients under GFD for at least 1 year were recruited. Non-celiac subjects (n = 8) were recruited as control group. Two biopsies of the cheek lining were taken from each subject for mRNA analysis and immunohistochemical characterization. We observed a significant decrease in the expression of epithelial junction proteins in all CD patients, indicating that oral mucosa barrier integrity is compromised. FoxP3+ population was greatly increased in CD patients, suggesting that Tregs are recruited to the damaged mucosa, even after avoidance of gluten. Amphiregulin mRNA levels from Peripheral Blood Mononuclear Cells (PBMCs) and epithelial damage in the oral mucosa correlated with Treg infiltration in all the experimental groups, suggesting that recruited Tregs might display a "repair" phenotype. Based on these results, we propose that oral mucosa is altered in CD and, as such, might have diagnostic potential. Furthermore, due to its tolerogenic nature, it could be an important target for oral immunotherapy.
乳糜泻（CD）是一种慢性自身免疫性疾病，其特征是在摄入麸质后发生免疫触发的肠病。目前唯一可用的治疗方法是终生无麸质饮食（GFD）。在 CD 中已经描述了几种肠外表现，其中一些会影响口腔黏膜。因此，我们假设口腔黏膜可能是新型生物标志物的潜在靶点，也是 CD 治疗的给药途径。我们招募了 6 名确诊和 7 名接受 GFD 治疗至少 1 年的 CD 患者，以及 8 名非乳糜泻患者作为对照组。从每位受试者中取出两个脸颊衬里的活检组织进行 mRNA 分析和免疫组织化学特征分析。我们观察到所有 CD 患者的上皮连接蛋白表达显著降低，这表明口腔黏膜屏障完整性受损。FoxP3+群体在 CD 患者中大大增加，这表明 Treg 被募集到受损的黏膜，即使在避免摄入麸质后也是如此。外周血单个核细胞（PBMCs）中的 Amphiregulin mRNA 水平和口腔黏膜上皮损伤与所有实验组中的 Treg 浸润相关，这表明募集的 Treg 可能表现出“修复”表型。基于这些结果，我们提出口腔黏膜在 CD 中发生改变，因此可能具有诊断潜力。此外，由于其耐受原性，它可能是口腔免疫治疗的重要靶点。
