Riaz Bushra, Ryu Hye-Myung, Choi Bunsoon, Sohn Seonghyang
Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 16499, Republic of Korea.
Department of Microbiology, Ajou University School of Medicine, Suwon 16499, Republic of Korea.
Pathogens. 2025 Apr 8;14(4):366. doi: 10.3390/pathogens14040366.
Eosinophils are granulocytes involved in the effector phase of type 2 T cell immune responses, which are elevated in inflammatory conditions like ulcerative colitis (UC) and other allergic diseases. UC is a chronic inflammatory colon disease, marked by excessive eosinophil infiltration and elevated Th2 cytokines, which contribute to mucosal inflammation and tissue damage. Dietary factors, including certain organic acids, can influence UC progression by modulating gut immune responses. This research is the first to explore the dose-dependent effects of tartaric acid (TA), a naturally occurring organic acid widely used in the food industry, on eosinophil activation and Th2 cytokine response in both normal mice and a dextran sulfate sodium (DSS)-induced colitis model. Normal mice were treated with TA at varying doses (5 µg, 25 µg, and 50 µg/mouse/day), while colitis mice received 50 µg TA. Eosinophil activation markers (CD11b+, SiglecF+, and CCR3+), Th2 cytokines (IL-4, IL-13, and IL-31), and IL-17 were assessed in peripheral blood leukocytes, lymph nodes, and splenocytes using flow cytometry. Additionally, mRNA expression levels of eosinophil-associated chemokines and cytokines in the splenocytes were quantified with real-time qPCR. Our results demonstrate a dose-dependent effect of TA, with the highest dose (50 µg) significantly increasing eosinophil activation markers, Th2 cytokines, IL-17, and mRNA expression of SiglecF, CCL11, and toll-like receptor 4 in normal mice. In colitis mice, treatment with 50 µg TA showed marked increases in IL-13 levels compared to those of untreated colitis mice, reflecting increased eosinophil recruitment to inflamed tissues. Moreover, mRNA expression of IL-5Rα was elevated in normal mice and colitis mice administered with TA. These results suggest that TA enhances eosinophil proliferation, the upregulation of their regulatory molecules, and Th2 immune profiles, potentially worsening the severity of colitis.
嗜酸性粒细胞是参与2型T细胞免疫反应效应阶段的粒细胞，在溃疡性结肠炎（UC）和其他过敏性疾病等炎症状态下数量会升高。UC是一种慢性炎症性结肠疾病，其特征是嗜酸性粒细胞过度浸润和Th2细胞因子升高，这会导致黏膜炎症和组织损伤。饮食因素，包括某些有机酸，可通过调节肠道免疫反应影响UC的进展。本研究首次探讨了酒石酸（TA）——一种在食品工业中广泛使用的天然有机酸——对正常小鼠和葡聚糖硫酸钠（DSS）诱导的结肠炎模型中嗜酸性粒细胞活化及Th2细胞因子反应的剂量依赖性影响。正常小鼠分别接受不同剂量（5微克、25微克和50微克/小鼠/天）的TA处理，而结肠炎小鼠接受50微克TA。使用流式细胞术评估外周血白细胞、淋巴结和脾细胞中的嗜酸性粒细胞活化标志物（CD11b+、SiglecF+和CCR3+）、Th2细胞因子（IL-4、IL-13和IL-31）以及IL-17。此外，通过实时定量PCR定量脾细胞中嗜酸性粒细胞相关趋化因子和细胞因子的mRNA表达水平。我们的结果证明了TA的剂量依赖性效应，最高剂量（50微克）显著增加了正常小鼠中的嗜酸性粒细胞活化标志物、Th2细胞因子、IL-17以及SiglecF、CCL11和Toll样受体4的mRNA表达。在结肠炎小鼠中，与未处理的结肠炎小鼠相比，50微克TA处理显示IL-13水平显著升高，反映出嗜酸性粒细胞向炎症组织的募集增加。此外，给予TA的正常小鼠和结肠炎小鼠中IL-5Rα的mRNA表达均升高。这些结果表明，TA增强了嗜酸性粒细胞的增殖、其调节分子的上调以及Th2免疫谱，可能会加重结肠炎的严重程度。
