{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:06:26Z","timestamp":1791497186614,"version":"4.3.4"},"reference-count":34,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011912","name":"Taipei Veterans General Hospital","doi-asserted-by":"publisher","award":["V108C-182"],"award-info":[{"award-number":["V108C-182"]}],"id":[{"id":"10.13039\/501100011912","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001868","name":"National Science Council","doi-asserted-by":"publisher","award":["NSC 102-2314-B-016 -054 -MY3"],"award-info":[{"award-number":["NSC 102-2314-B-016 -054 -MY3"]}],"id":[{"id":"10.13039\/501100001868","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Mounting evidence demonstrates that a high-salt diet (HSD) not only affects hemodynamic changes but also disrupts immune homeostasis. The T helper 17 (Th17) and regulatory T cells (Tregs) are susceptible to hypersalinity. However, research on the influence of sodium on Th2-mediated food allergies remains scarce. We aimed to investigate the effect of dietary sodium on the immune response to food allergies. Mice maintained on an HSD (4% NaCl), low-salt diet (LSD; 0.4% NaCl), or control diet (CTRL; 1.0% NaCl) were orally sensitized with ovalbumin (OVA) and a cholera toxin (CT) adjuvant, and then subjected to an intragastric OVA challenge. OVA-specific immunoglobulin G (IgG), IgG1, IgG2a, and IgE antibodies were significantly higher in the HSD group than in the CTRL group (p &lt; 0.001, p &lt; 0.05, p &lt; 0.01, and p &lt; 0.05, respectively). Mice on HSD had significantly higher interleukin (IL)-4 levels than the CTRL group (p &lt; 0.01). The IL-10 levels were significantly lower in the HSD group than in the CTRL group (p &lt; 0.05). The serum levels of interferon-\u03b3 (IFN-\u03b3), sodium, and chloride did not differ among the three groups. This study indicates that excessive salt intake promotes Th2 responses in a mouse model of food allergy.<\/jats:p>","DOI":"10.3390\/nu13113684","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T21:31:26Z","timestamp":1634765486000},"page":"3684","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["A High-Sodium Diet Modulates the Immune Response of Food Allergy in a Murine Model"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7654-6873","authenticated-orcid":false,"given":"Zheying","family":"Liu","sequence":"first","affiliation":[{"name":"Emergency Department, Department of Emergency and Critical Medicine, Wan Fang Hospital, Taipei Medical University, Taipei City 11696, Taiwan"},{"name":"Department of Emergency, School of Medicine, College of Medicine, Taipei Medical University, Taipei City 11031, Taiwan"},{"name":"Department of Pediatrics, Wan Fang Hospital, Taipei Medical University, Taipei City 11696, Taiwan"},{"name":"Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Taipei Veterans General Hospital, Taipei City 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Kuan","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Taipei Veterans General Hospital, Taipei City 11217, Taiwan"},{"name":"Department of Pediatrics, Yonghe Cardinal Tien Hospital, New Taipei City 23445, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3469-7638","authenticated-orcid":false,"given":"Chih-Kang","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Taipei Veterans General Hospital, Taipei City 11217, Taiwan"},{"name":"Department of Pediatrics, Taipei Veterans General Hospital, Taoyuan Branch, Taoyuan City 33052, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Feng","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Taipei Veterans General Hospital, Taipei City 11217, Taiwan"},{"name":"National Defense Medical Center, School of Medicine, Taipei City 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1161\/HYPERTENSIONAHA.118.11128","article-title":"Salt intake and immunity","volume":"72","author":"Afsar","year":"2018","journal-title":"Hypertension"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/nature11868","article-title":"Sodium chloride drives autoimmune disease by the induction of pathogenic TH 17 cells","volume":"496","author":"Kleinewietfeld","year":"2013","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/nature11984","article-title":"Induction of pathogenic TH 17 cells by inducible salt-sensing kinase SGK1","volume":"496","author":"Wu","year":"2013","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1016\/j.autrev.2018.05.007","article-title":"The role of dietary sodium in autoimmune diseases: The salty truth","volume":"17","author":"Sharif","year":"2018","journal-title":"Autoimmun. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/nature06878","article-title":"TGF-\u03b2-induced Foxp3 inhibits TH 17 cell differentiation by antagonizing ROR\u03b3t function","volume":"453","author":"Zhou","year":"2008","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4212","DOI":"10.1172\/JCI81151","article-title":"Sodium chloride inhibits the suppressive function of FOXP3+ regulatory T cells","volume":"125","author":"Hernandez","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1084\/jem.20032058","article-title":"Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells","volume":"199","author":"Akdis","year":"2004","journal-title":"J. Exp. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/nm.2754","article-title":"Therapies for allergic inflammation: Refining strategies to induce tolerance","volume":"18","author":"Akdis","year":"2012","journal-title":"Nat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.immuni.2015.02.004","article-title":"Regulatory T cell reprogramming toward a Th2-cell-like lineage impairs oral tolerance and promotes food allergy","volume":"42","author":"Rivas","year":"2015","journal-title":"Immunity"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Abbring, S., Wolf, J., Ayechu-Muruzabal, V., Diks, M.A.P., Alhamwe, B.A., Alhamdan, F., Harb, H., Renz, H., Garn, H., and Garssen, J. (2019). Raw Cow\u2019s Milk Reduces Allergic Symptoms in a Murine Model for Food Allergy-A Potential Role For Epigenetic Modifications. Nutrients, 11.","DOI":"10.3390\/nu11081721"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3193","DOI":"10.3390\/nu12103193","article-title":"Decreased Histone Acetylation Levels at Th1 and Regulatory Loci after Induction of Food Allergy","volume":"12","author":"Meulenbroek","year":"2020","journal-title":"Nutrients"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1038\/s41581-019-0167-y","article-title":"The role of sodium in modulating immune cell function","volume":"15","author":"Wilck","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.jaci.2017.11.003","article-title":"Food allergy: A review and update on epidemiology, pathogenesis, diagnosis, prevention, and management","volume":"141","author":"Sicherer","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.jaci.2011.01.039","article-title":"Prevalence of challenge-proven IgE-mediated food allergy using population-based sampling and predetermined challenge criteria in infants","volume":"127","author":"Osborne","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/nri3830","article-title":"The impact of diet on asthma and allergic diseases","volume":"15","author":"Julia","year":"2015","journal-title":"Nat. Rev. Immunol"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Acevedo, N., Alashkar Alhamwe, B., Caraballo, L., Ding, M., Ferrante, A., Garn, H., Garssen, J., Hii, C.S., Irvine, J., and Llinas-Caballero, K. (2021). Perinatal and Early-Life Nutrition, Epigenetics, and Allergy. Nutrients, 13.","DOI":"10.3390\/nu13030724"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.3389\/fimmu.2020.02141","article-title":"The Impact of Milk and Its Components on Epigenetic Programming of Immune Function in Early Life and Beyond: Implications for Allergy and Asthma","volume":"11","author":"Porbahaie","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/S1081-1206(10)60570-4","article-title":"Effect of sublingual administration with a native or denatured protein allergen and adjuvant CpG oligodeoxynucleotides or cholera toxin on systemic TH2 immune responses and mucosal immunity in mice","volume":"99","author":"Huang","year":"2007","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.fct.2009.01.017","article-title":"Dietary perilla oil lowers serum lipids and ovalbumin-specific IgG1, but increases total IgE levels in ovalbumin-challenged mice","volume":"47","author":"Chang","year":"2009","journal-title":"Food Chem. Toxicol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.biopha.2018.02.061","article-title":"Polysaccharide isolated from Aloe vera gel suppresses ovalbumin-induced food allergy through inhibition of Th2 immunity in mice","volume":"101","author":"Lee","year":"2018","journal-title":"Biomed Pharm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1186\/s12931-014-0142-x","article-title":"Food allergy enhances allergic asthma in mice","volume":"15","author":"Bouchaud","year":"2014","journal-title":"Respir. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1186\/s12974-017-0954-y","article-title":"Impact of combined sodium chloride and saturated long-chain fatty acid challenge on the differentiation of T helper cells in neuroinflammation","volume":"14","author":"Hammer","year":"2017","journal-title":"J. Neuroinflammation"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"eaau0683","DOI":"10.1126\/scitranslmed.aau0683","article-title":"Sodium chloride is an ionic checkpoint for human TH2 cells and shapes the atopic skin microenvironment","volume":"11","author":"Matthias","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1248\/bpb.18.854","article-title":"Oral tolerance to ovalbumin in mice as a model for detecting modulators of the immunologic tolerance to a specific antigen","volume":"18","author":"KIM","year":"1995","journal-title":"Biol. Pharm. Bull."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1111\/j.1365-2222.2008.03194.x","article-title":"Animal models of protein allergenicity: Potential benefits, pitfalls and challenges","volume":"39","author":"Dearman","year":"2009","journal-title":"Clin. Exp. Allergy"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1111\/j.1365-2222.2007.02681.x","article-title":"CD4+ CD25+ T cells regulate the intensity of hypersensitivity responses to peanut, but are not decisive in the induction of oral sensitization","volume":"37","author":"Wehrens","year":"2007","journal-title":"Clin. Exp. Allergy"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/S0091-6749(03)01869-4","article-title":"Regulatory T cells control the development of allergic disease and asthma","volume":"112","author":"Umetsu","year":"2003","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/s41577-018-0113-4","article-title":"Sodium in the microenvironment regulates immune responses and tissue homeostasis","volume":"19","author":"Muller","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"647","DOI":"10.4049\/jimmunol.153.2.647","article-title":"Production of IgE antibody and allergic sensitization of intestinal and peripheral tissues after oral immunization with protein Ag and cholera toxin","volume":"153","author":"Snider","year":"1994","journal-title":"J. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1002\/1521-4141(200007)30:7<1861::AID-IMMU1861>3.0.CO;2-A","article-title":"CD19-deficient mice exhibit poor responsiveness to oral immunization despite evidence of unaltered total IgA levels, germinal centers and IgA-isotype switching in Peyer\u2019s patches","volume":"30","author":"Lycke","year":"2000","journal-title":"Eur. J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1002\/(SICI)1521-4141(199906)29:06<1774::AID-IMMU1774>3.0.CO;2-1","article-title":"The mucosal adjuvant effects of cholera toxin and immune-stimulating complexes differ in their requirement for IL-12, indicating different pathways of action","volume":"29","author":"Grdic","year":"1999","journal-title":"Eur. J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zielinski, C.E. (2021). Regulation of T Cell Responses by Ionic Salt Signals. Cells, 10.","DOI":"10.3390\/cells10092365"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.it.2021.04.002","article-title":"Sodium and its manifold impact on our immune system","volume":"42","author":"Jobin","year":"2021","journal-title":"Trends Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.4049\/jimmunol.1700356","article-title":"Dietary salt exacerbates experimental colitis","volume":"199","author":"Tubbs","year":"2017","journal-title":"J. Immunol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/11\/3684\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:19:32Z","timestamp":1760167172000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/11\/3684"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,20]]},"references-count":34,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["nu13113684"],"URL":"https:\/\/doi.org\/10.3390\/nu13113684","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,20]]}}}