Tartaric Acid Exacerbates DSS-Induced Colitis by Promoting Eosinophilic Inflammation via IL-13 and IL-5Rα Upregulation

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...

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Main Authors: Bushra Riaz, Hye-Myung Ryu, Bunsoon Choi, Seonghyang Sohn
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Pathogens
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Online Access:https://www.mdpi.com/2076-0817/14/4/366
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author Bushra Riaz
Hye-Myung Ryu
Bunsoon Choi
Seonghyang Sohn
author_facet Bushra Riaz
Hye-Myung Ryu
Bunsoon Choi
Seonghyang Sohn
author_sort Bushra Riaz
collection DOAJ
description 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.
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spelling doaj-art-715cebfa0ceb48d091653550a370a8132025-08-20T02:18:15ZengMDPI AGPathogens2076-08172025-04-0114436610.3390/pathogens14040366Tartaric Acid Exacerbates DSS-Induced Colitis by Promoting Eosinophilic Inflammation via IL-13 and IL-5Rα UpregulationBushra Riaz0Hye-Myung Ryu1Bunsoon Choi2Seonghyang Sohn3Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 16499, Republic of KoreaDepartment of Microbiology, Ajou University School of Medicine, Suwon 16499, Republic of KoreaInstitute of Medical Science, Ajou University School of Medicine, Suwon 16499, Republic of KoreaDepartment of Biomedical Sciences, Ajou University School of Medicine, Suwon 16499, Republic of KoreaEosinophils 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.https://www.mdpi.com/2076-0817/14/4/366eosinophilsTh2 cytokinestartaric acidcolitismouse model
spellingShingle Bushra Riaz
Hye-Myung Ryu
Bunsoon Choi
Seonghyang Sohn
Tartaric Acid Exacerbates DSS-Induced Colitis by Promoting Eosinophilic Inflammation via IL-13 and IL-5Rα Upregulation
Pathogens
eosinophils
Th2 cytokines
tartaric acid
colitis
mouse model
title Tartaric Acid Exacerbates DSS-Induced Colitis by Promoting Eosinophilic Inflammation via IL-13 and IL-5Rα Upregulation
title_full Tartaric Acid Exacerbates DSS-Induced Colitis by Promoting Eosinophilic Inflammation via IL-13 and IL-5Rα Upregulation
title_fullStr Tartaric Acid Exacerbates DSS-Induced Colitis by Promoting Eosinophilic Inflammation via IL-13 and IL-5Rα Upregulation
title_full_unstemmed Tartaric Acid Exacerbates DSS-Induced Colitis by Promoting Eosinophilic Inflammation via IL-13 and IL-5Rα Upregulation
title_short Tartaric Acid Exacerbates DSS-Induced Colitis by Promoting Eosinophilic Inflammation via IL-13 and IL-5Rα Upregulation
title_sort tartaric acid exacerbates dss induced colitis by promoting eosinophilic inflammation via il 13 and il 5rα upregulation
topic eosinophils
Th2 cytokines
tartaric acid
colitis
mouse model
url https://www.mdpi.com/2076-0817/14/4/366
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AT bunsoonchoi tartaricacidexacerbatesdssinducedcolitisbypromotingeosinophilicinflammationviail13andil5raupregulation
AT seonghyangsohn tartaricacidexacerbatesdssinducedcolitisbypromotingeosinophilicinflammationviail13andil5raupregulation