{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T01:44:08Z","timestamp":1782351848144,"version":"3.54.5"},"reference-count":40,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2013,5,2]],"date-time":"2013-05-02T00:00:00Z","timestamp":1367452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Fluoride is an environmental and industrial pollutant that affects various organs in humans and animals. The cecal tonsil is an important component of the mucosal immune system and performs important and unique immune functions. In the present study, we investigated the effects of dietary high fluorine on the quantities of IgA+ B cells in the cecal tonsil by immunohistochemistry, and the immunoglobulin A (IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM) contents in the cecal tonsil by ELISA. A total of 280 one-day-old avian broilers were divided into four groups and fed on a corn-soybean basal diet as control diet (fluorine 22.6 mg\/kg) or the same diet supplemented with 400, 800 and 1,200 mg\/kg fluorine (high fluorine groups I, II and III) in the form of sodium fluoride, respectively, throughout a 42-day experimental period. The results showed that the quantities of IgA+ B cells were lower (p &lt; 0.05 or p &lt; 0.01) and the IgA, IgG, and IgM contents were decreased (p &lt; 0.05 or p &lt; 0.01) in high fluorine groups II and III in comparison with those of control group. It was concluded that dietary fluorine, in the  800\u20131,200 mg\/kg range, could reduce the numbers of the IgA+ B cells and immunoglobulin contents in the cecal tonsil, implying the local mucosal immune function was ultimately impacted in broilers.<\/jats:p>","DOI":"10.3390\/ijerph10051775","type":"journal-article","created":{"date-parts":[[2013,5,2]],"date-time":"2013-05-02T11:24:57Z","timestamp":1367493897000},"page":"1775-1785","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Decreased IgA+ B Cells Population and IgA, IgG, IgM Contents of the Cecal Tonsil Induced by Dietary High Fluorine in Broilers"],"prefix":"10.3390","volume":"10","author":[{"given":"Juan","family":"Liu","sequence":"first","affiliation":[{"name":"Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2963-531X","authenticated-orcid":false,"given":"Hengmin","family":"Cui","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Peng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Fang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhicai","family":"Zuo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junliang","family":"Deng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hesong","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bangyuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanxin","family":"Deng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangping","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2013,5,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1016\/j.fct.2009.02.008","article-title":"Effects of sodium fluoride exposure on some biochemical parameters in mice: Evaluation of the ameliorative effect of royal jelly applications on these parameters","volume":"47","author":"Kanbur","year":"2009","journal-title":"Food Chem. Toxicol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1016\/S0043-1354(97)00357-6","article-title":"Defluoridation of septentrional Sahara water of North Africa by electrocoagulation process using bipolar aluminium electrodes","volume":"32","author":"Mameri","year":"1998","journal-title":"Water Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1016\/j.ecoenv.2009.08.014","article-title":"The association between osteocalcin gene polymorphism and dental fluorosis among children exposed to fluoride in People\u2019s Republic of China","volume":"72","author":"Ba","year":"2009","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s10021-002-0211-8","article-title":"A geochemical trophic cascade in Yellow stone\u2019s geothermal environments","volume":"5","author":"Garrott","year":"2002","journal-title":"Ecosystems"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1081\/IPH-120018287","article-title":"Effect of sodium fluoride on the murine splenic immune response to porphyromonas gingivalis in vitro","volume":"25","author":"Sosroseno","year":"2003","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1210\/jcem-68-1-150","article-title":"Safe and effective treatment of osteoporosis with intermittent slow release of sodium fluoride: Augmentation of vertebral bone mass and inhibition of fractures","volume":"68","author":"Pak","year":"1989","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1177\/00220345920710051901","article-title":"Acute and chronic fluoride toxicity","volume":"71","author":"Whitford","year":"1992","journal-title":"J. Dent. Res."},{"key":"ref_8","first-page":"111","article-title":"Effect of fluoride on immune system function","volume":"6","author":"Gibson","year":"1992","journal-title":"Complement. Med. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s12011-012-9333-9","article-title":"The influence of fluoride on the expression of inhibitors of Wnt\/\u03b2-Catenin signaling pathway in rat skin fibroblast cells","volume":"148","author":"Liu","year":"2012","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s12011-009-8599-z","article-title":"Effect of high fluoride on the cell cycle and apoptosis of renal cells in chickens","volume":"138","author":"Bai","year":"2010","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s12011-011-9194-7","article-title":"Protective effects of curcumin against sodium fluoride-induced toxicity in rat kidneys","volume":"145","author":"Nabavi","year":"2012","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1177\/0960327110388538","article-title":"Decreased antioxidase activities and oxidative stress in the spleen of chickens fed on high-fluorine diets","volume":"30","author":"Chen","year":"2010","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1177\/0960327110379022","article-title":"Cell-cycle blockage associated with increased apoptotic cells in the thymus of chickens fed on diets high in fluorine","volume":"30","author":"Chen","year":"2010","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1007\/s12011-009-8373-2","article-title":"Decreased percentages of the peripheral blood T-cell subsets and the serum IL-2 contents in chickens fed on diets excess in fluorine","volume":"132","author":"Chen","year":"2009","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s12011-010-8733-y","article-title":"Effect of pineal proteins at different dose level on fluoride-induced changes in plasma biochemical and blood antioxidants enzymes in rats","volume":"141","author":"Bharti","year":"2012","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s12011-011-9251-2","article-title":"Influence of methionine and vitamin E on fluoride concentration in bones and teeth of rats exposed to sodium fluoride in drinking water","volume":"146","author":"Blaszczyk","year":"2012","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/0014-4800(90)90025-9","article-title":"Aortic calcification in chronic fluoride poisoning: Biochemical electron microscopic evidence","volume":"53","author":"Susheela","year":"1990","journal-title":"Exp. Mol. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1155\/2000\/219623","article-title":"Effects of sodium fluoride on water and acid secretion, soluble mucus and adherent mucus of the rat stomach","volume":"14","author":"Gharzouli","year":"2010","journal-title":"Can. J. Gastroenterol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1128\/CMR.9.3.349","article-title":"Avian gut-associated lymphoid tissues and intestinal immune responses to Eimeria parasites","volume":"9","author":"Lillehoj","year":"1996","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_20","first-page":"47","article-title":"Dietary high fluorine induces oxidative damage in the cecal tonsil of broilers","volume":"45","author":"Liu","year":"2012","journal-title":"Fluoride"},{"key":"ref_21","first-page":"53","article-title":"Decreased percentages of T-cell subsets and IL-2 contents in the cecal tonsil of broilers fed diets high in fluorine","volume":"45","author":"Liu","year":"2012","journal-title":"Fluoride"},{"key":"ref_22","unstructured":"(1994). Subcommittee on Poultry Nutrition, Committee on Animal Nutrition, Board on Agriculture, National Research Council\u2014Ninth Revised Edition, National Academy Press."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/S0168-8278(99)80139-1","article-title":"Human and rat hepatic stellate cells produce stem cell factor: A possible mechanism for mast cell recruitment in liver fibrosis","volume":"30","author":"Gaca","year":"1999","journal-title":"J. Hepatol."},{"key":"ref_24","first-page":"141","article-title":"Mucosal responses to parenteral and mucosal vaccines","volume":"95","author":"Kaul","year":"1998","journal-title":"Dev. Biol. Stand."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.immuni.2008.05.001","article-title":"The biology of intestinal immunoglobulin A responses","volume":"28","author":"Cerutti","year":"2008","journal-title":"Immunity"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2793","DOI":"10.4049\/jimmunol.175.5.2793","article-title":"Secretory IgA possesses intrinsic modulatory properties stimulating mucosal and systemic immune responses","volume":"175","author":"Favre","year":"2005","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/0167-5699(93)90245-G","article-title":"A three-tiered view of the role of IgA in mucosal defense","volume":"14","author":"Mazanec","year":"1993","journal-title":"Immunol. Today"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6901","DOI":"10.1073\/pnas.89.15.6901","article-title":"Intracellular neutralization of virus by immunoglobulin A antibodies","volume":"89","author":"Mazanec","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1172\/JCI6310","article-title":"Killing of Streptococcus pneumoniae by capsular polysaccharide-specific polymeric IgA, complement, and phagocytes","volume":"104","author":"Janoff","year":"1999","journal-title":"J. Clin. Invest."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1042\/bj20040200","article-title":"A functional polymeric immunoglobulin receptor in chicken (Gallus gallus) indicates ancient role of secretory IgA in mucosal immunity","volume":"380","author":"Wieland","year":"2004","journal-title":"Biochem. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/nri1057","article-title":"Anatomical basis of tolerance and immunity to intestinal antigens","volume":"3","author":"Mowat","year":"2003","journal-title":"Nature Rev. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1053\/tgie.2001.19906","article-title":"Importance of enteral feeding in maintaining gut integrity","volume":"3","author":"Kudsk","year":"2001","journal-title":"Tech. Gastrointest. Endosc."},{"key":"ref_33","first-page":"102","article-title":"Changes induced by high dietary fluorine in the cecal tonsil cytokine content of broilers","volume":"45","author":"Liu","year":"2012","journal-title":"Fluoride"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.it.2009.02.001","article-title":"Do we have memory of danger as well as antigen?","volume":"30","author":"Noble","year":"2009","journal-title":"Trends Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4049\/jimmunol.110.1.1","article-title":"Studies on the secretory immunologic system of fowl. III. Serum and secretory IgA of the chicken","volume":"110","author":"Leslie","year":"1973","journal-title":"J. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"855","DOI":"10.4049\/jimmunol.149.3.855","article-title":"Chicken IgA H chains. Implications concerning the evolution of H chain genes","volume":"149","author":"Mansikka","year":"1992","journal-title":"J. Immunol."},{"key":"ref_37","first-page":"30","article-title":"The immune toxicity of fluoride","volume":"17","author":"Zhang","year":"2002","journal-title":"Chin. J. Ctrl. End."},{"key":"ref_38","first-page":"325","article-title":"The changes of serum IgA, IgG, and IgM content in fluoride exposed worker","volume":"9","author":"Shen","year":"1996","journal-title":"Chin. J. Ind. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0013-9351(87)80091-9","article-title":"Effect of sodium fluoride on antibody formation in rabbits","volume":"44","author":"Jain","year":"1987","journal-title":"Environ. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s12011-012-9595-2","article-title":"Dietary high fluorine induces apoptosis and alters bcl-2,bax, and caspase-3 protein expression in the cecal tonsil lymphocytes of broilers","volume":"152","author":"Liu","year":"2013","journal-title":"Biol. Trace Elem. Res."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/10\/5\/1775\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:46:30Z","timestamp":1760219190000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/10\/5\/1775"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5,2]]},"references-count":40,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2013,5]]}},"alternative-id":["ijerph10051775"],"URL":"https:\/\/doi.org\/10.3390\/ijerph10051775","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,5,2]]}}}