{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T17:21:55Z","timestamp":1785777715773,"version":"3.56.0"},"reference-count":100,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T00:00:00Z","timestamp":1596499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012524","name":"American Lebanese Syrian Associated Charities","doi-asserted-by":"publisher","award":["ALSAC"],"award-info":[{"award-number":["ALSAC"]}],"id":[{"id":"10.13039\/100012524","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA21765"],"award-info":[{"award-number":["P30CA21765"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Vitamin A is an important regulator of immune protection, but it is often overlooked in studies of infectious disease. Vitamin A binds an array of nuclear receptors (e.g., retinoic acid receptor, peroxisome proliferator-activated receptor, retinoid X receptor) and influences the barrier and immune cells responsible for pathogen control. Children and adults in developed and developing countries are often vitamin A-deficient or insufficient, characteristics associated with poor health outcomes. To gain a better understanding of the protective mechanisms influenced by vitamin A, we examined immune factors and epithelial barriers in vitamin A deficient (VAD) mice, vitamin D deficient (VDD) mice, double deficient (VAD+VDD) mice, and mice on a vitamin-replete diet (controls). Some mice received insults, including intraperitoneal injections with complete and incomplete Freund\u2019s adjuvant (emulsified with PBS alone or with DNA + Fus-1 peptide) or intranasal inoculations with Sendai virus (SeV). Both before and after insults, the VAD and VAD+VDD mice exhibited abnormal serum immunoglobulin isotypes (e.g., elevated IgG2b levels, particularly in males) and cytokine\/chemokine patterns (e.g., elevated eotaxin). Even without insult, when the VAD and VAD+VDD mice reached 3\u20136 months of age, they frequently exhibited opportunistic ascending bacterial urinary tract infections. There were high frequencies of nephropathy (squamous cell hyperplasia of the renal urothelium, renal scarring, and ascending pyelonephritis) and death in the VAD and VAD+VDD mice. When younger VAD mice were infected with SeV, the predominant lesion was squamous cell metaplasia of respiratory epithelium in lungs and bronchioles. Results highlight a critical role for vitamin A in the maintenance of healthy immune responses, epithelial cell integrity, and pathogen control.<\/jats:p>","DOI":"10.3390\/ijms21155570","type":"journal-article","created":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T10:45:17Z","timestamp":1596537917000},"page":"5570","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Consequences of Vitamin A Deficiency: Immunoglobulin Dysregulation, Squamous Cell Metaplasia, Infectious Disease, and Death"],"prefix":"10.3390","volume":"21","author":[{"given":"Sherri L.","family":"Surman","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5317-1055","authenticated-orcid":false,"given":"Rhiannon R.","family":"Penkert","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E.","family":"Sealy","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart G.","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6570-7179","authenticated-orcid":false,"given":"Tony N.","family":"Marion","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Vogel","sequence":"additional","affiliation":[{"name":"Department of Pathology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia L.","family":"Hurwitz","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"},{"name":"Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1056\/NEJM199007193230304","article-title":"A randomized, controlled trial of vitamin A in children with severe measles","volume":"323","author":"Hussey","year":"1990","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3389\/fpubh.2018.00013","article-title":"National Immunization Campaigns with Oral Polio Vaccine Reduce All-Cause Mortality: A Natural Experiment within Seven Randomized Trials","volume":"6","author":"Andersen","year":"2018","journal-title":"Front. Public Health"},{"key":"ref_3","unstructured":"(2013). Vitamin A supplementation: Who, when and how. Community Eye Health, 26, 71."},{"key":"ref_4","first-page":"65","article-title":"What is vitamin A and why do we need it?","volume":"26","author":"Gilbert","year":"2013","journal-title":"Community Eye Health"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1093\/infdis\/167.5.1003","article-title":"Vitamin A, infectious disease, and childhood mortality: A 2 solution?","volume":"167","author":"Sommer","year":"1993","journal-title":"J. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/cei.12718","article-title":"Retinol binding protein and vitamin D associations with serum antibody isotypes, serum influenza virus-specific neutralizing activities and airway cytokine profiles","volume":"183","author":"Jones","year":"2016","journal-title":"Clin. Exp. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.jpeds.2017.04.061","article-title":"Low Retinol-Binding Protein and Vitamin D Levels Are Associated with Severe Outcomes in Children Hospitalized with Lower Respiratory Tract Infection and Respiratory Syncytial Virus or Human Metapneumovirus Detection","volume":"187","author":"Hurwitz","year":"2017","journal-title":"J. Pediatr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/nri2378","article-title":"Vitamin effects on the immune system: Vitamins A and D take centre stage","volume":"8","author":"Mora","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.immuni.2004.10.002","article-title":"Retinoic acid: An educational \u201cvitamin elixir\u201d for gut-seeking T cells","volume":"21","author":"Mora","year":"2004","journal-title":"Immunity"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cyto.2016.11.015","article-title":"Vitamin A differentially regulates cytokine expression in respiratory epithelial and macrophage cell lines","volume":"91","author":"Penkert","year":"2017","journal-title":"Cytokine"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.cell.2014.03.012","article-title":"Nuclear Receptors, RXR, and the Big Bang","volume":"157","author":"Evans","year":"2014","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2924","DOI":"10.1096\/fasebj.5.14.1661245","article-title":"Retinoids and their receptors in differentiation, embryogenesis, and neoplasia","volume":"5","year":"1991","journal-title":"FASEB J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"41589","DOI":"10.1074\/jbc.C300368200","article-title":"Retinoic acid is a high affinity selective ligand for the peroxisome proliferator-activated receptor beta\/delta","volume":"278","author":"Shaw","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/978-94-024-0945-1_2","article-title":"Functions of Intracellular Retinoid Binding-Proteins","volume":"81","author":"Napoli","year":"2016","journal-title":"Subcell Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1089\/vim.2015.0104","article-title":"Hotspots for Vitamin-Steroid-Thyroid Hormone Response Elements Within Switch Regions of Immunoglobulin Heavy Chain Loci Predict a Direct Influence of Vitamins and Hormones on B Cell Class Switch Recombination","volume":"29","author":"Hurwitz","year":"2016","journal-title":"Viral Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Jones, B.G., Sealy, R.E., Penkert, R.R., Surman, S.L., Maul, R.W., Neale, G., Xu, B., Gearhart, P.J., and Hurwitz, J.L. (2018). Complex sex-biased antibody responses: Estrogen receptors bind estrogen response elements centered within immunoglobulin heavy chain gene enhancers. Int. Immunol.","DOI":"10.1093\/intimm\/dxy074"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.molimm.2016.07.015","article-title":"Binding of estrogen receptors to switch sites and regulatory elements in the immunoglobulin heavy chain locus of activated B cells suggests a direct influence of estrogen on antibody expression","volume":"77","author":"Jones","year":"2016","journal-title":"Mol. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Sealy, R.E., Jones, B.G., Surman, S.L., Penkert, R.R., Pelletier, S., Neale, G., and Hurwitz, J.L. (2019). Will Attention by Vaccine Developers to the Host\u2019s Nuclear Hormone Levels and Immunocompetence Improve Vaccine Success?. Vaccines (Basel), 7.","DOI":"10.3390\/vaccines7010026"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5370","DOI":"10.4049\/jimmunol.1401849","article-title":"IgH chain class switch recombination: Mechanism and regulation","volume":"193","author":"Stavnezer","year":"2014","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3389\/fimmu.2014.00163","article-title":"Epigenetic Regulation of Individual Modules of the immunoglobulin heavy chain locus 3\u2032 Regulatory Region","volume":"5","author":"Birshtein","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1189\/jlb.70.6.849","article-title":"Modes of action of Freund\u2019s adjuvants in experimental models of autoimmune diseases","volume":"70","author":"Billiau","year":"2001","journal-title":"J. Leukoc. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.4049\/jimmunol.151.3.1614","article-title":"Antigen-specific induction of antibodies against native mammalian DNA in nonautoimmune mice","volume":"151","author":"Desai","year":"1993","journal-title":"J. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1093\/intimm\/12.11.1569","article-title":"Induction of anti-DNA antibody with DNA-peptide complexes","volume":"12","author":"Desai","year":"2000","journal-title":"Int. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/ki.2011.484","article-title":"Anti-DNA autoantibodies initiate experimental lupus nephritis by binding directly to the glomerular basement membrane in mice","volume":"82","author":"Krishnan","year":"2012","journal-title":"Kidney Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1111\/j.1460-9568.1996.tb01225.x","article-title":"Macrophage inflammatory protein-1beta (MIP-1beta) produced endogenously in brain during E. coli fever in rats","volume":"8","author":"Minano","year":"1996","journal-title":"Eur. J. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Heslop, R., Bojang, A.L., Jarju, S., Mendy, J., Mulwa, S., Secka, O., Mendy, F.S., Owolabi, O., Kampmann, B., and Sutherland, J.S. (2016). Changes in Host Cytokine Patterns of TB Patients with Different Bacterial Loads Detected Using 16S rRNA Analysis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0168272"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3062","DOI":"10.1128\/iai.64.8.3062-3068.1996","article-title":"Induction of cytokine granulocyte-macrophage colony-stimulating factor and chemokine macrophage inflammatory protein 2 mRNAs in macrophages by Legionella pneumophila or Salmonella typhimurium attachment requires different ligand-receptor systems","volume":"64","author":"Yamamoto","year":"1996","journal-title":"Infect. Immun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1165\/rcmb.2007-0173OC","article-title":"Secretion of IL-13 by airway epithelial cells enhances epithelial repair via HB-EGF","volume":"38","author":"Allahverdian","year":"2008","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4009","DOI":"10.1021\/bi962094o","article-title":"Cellular retinoic acid-binding protein(II) presence in rat uterine epithelial cells correlates with their synthesis of retinoic acid","volume":"36","author":"Bucco","year":"1997","journal-title":"Biochemistry"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Rudraraju, R., Jones, B.G., Surman, S.L., Sealy, R.E., Thomas, P.G., and Hurwitz, J.L. (2014). Respiratory tract epithelial cells express retinaldehyde dehydrogenase ALDH1A and enhance IgA production by stimulated B cells in the presence of vitamin A. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0086554"},{"key":"ref_31","first-page":"L71","article-title":"Retinoic acid-induced proliferation of lung alveolar epithelial cells: Relation with the IGF system","volume":"275","author":"Nabeyrat","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/S0022-3476(79)80790-8","article-title":"Xerophthalmia, protein-calorie malnutrition, and infections in children","volume":"95","author":"Brown","year":"1979","journal-title":"J. Pediatr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1136\/bmj.297.6652.834","article-title":"Increased bacterial binding to respiratory epithelial cells in vitamin A deficiency","volume":"297","author":"Chandra","year":"1988","journal-title":"Bmj"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/S0022-3476(33)80022-9","article-title":"Vitamin A deficiency in infants: A clinical and pathological study","volume":"3","author":"Blackfan","year":"1933","journal-title":"J. Pediatr."},{"key":"ref_35","first-page":"307","article-title":"Vitamin A","volume":"82","author":"Pinnock","year":"1991","journal-title":"Nurs. J. India"},{"key":"ref_36","first-page":"825","article-title":"Mortality associated with mild, untreated xerophthalmia","volume":"81","author":"Sommer","year":"1983","journal-title":"Trans. Am. Ophthalmol. Soc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1093\/ajcn\/40.5.1090","article-title":"Increased risk of respiratory disease and diarrhea in children with preexisting mild vitamin A deficiency","volume":"40","author":"Sommer","year":"1984","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Bloch, C.E. (1924). Further clinical investigations into the diseases arising in consequence of a deficiency in the fat-soluble A factor. Am. J. Dis. Child., 659\u2013667.","DOI":"10.1001\/archpedi.1924.04120240002001"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1046\/j.1464-410x.1999.00063.x","article-title":"The role of vitamin A in preventing renal scarring secondary to pyelonephritis","volume":"83","author":"Kavukcu","year":"1999","journal-title":"BJU Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1542\/peds.2010-0685","article-title":"Risk of renal scarring in children with a first urinary tract infection: A systematic review","volume":"126","author":"Shaikh","year":"2010","journal-title":"Pediatrics"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s00467-012-2334-2","article-title":"Can postpyelonephritic renal scarring be prevented?","volume":"28","author":"Neveus","year":"2013","journal-title":"Pediatr. Nephrol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.juro.2008.09.039","article-title":"Incidence of post-pyelonephritic renal scarring: A meta-analysis of the dimercapto-succinic acid literature","volume":"181","author":"Faust","year":"2009","journal-title":"J. Urol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0140-6736(96)06126-0","article-title":"Are younger children at highest risk of renal sequelae after pyelonephritis?","volume":"349","author":"Benador","year":"1997","journal-title":"Lancet"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1136\/adc.70.2.111","article-title":"Renal scarring after acute pyelonephritis","volume":"70","author":"Jakobsson","year":"1994","journal-title":"Arch. Dis. Child."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1136\/adc.78.3.271","article-title":"Serum vitamin A and beta-carotene concentrations and renal scarring in urinary tract infections","volume":"78","author":"Kavukcu","year":"1998","journal-title":"Arch. Dis. Child."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1007\/s004670100606","article-title":"Could the effective mechanisms of retinoids on nephrogenesis be also operative on the amelioration of injury in acquired renal lesions?","volume":"16","author":"Kavukcu","year":"2001","journal-title":"Pediatr. Nephrol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1111\/j.1442-200X.2007.02370.x","article-title":"Adjuvant effect of vitamin A on recurrent lower urinary tract infections","volume":"49","author":"Yilmaz","year":"2007","journal-title":"Pediatr. Int."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1093\/ndt\/16.3.441","article-title":"Potential role of retinoids in the therapy of renal disease","volume":"16","author":"Wagner","year":"2001","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s00467-012-2308-4","article-title":"The effect of vitamin E or vitamin A on the prevention of renal scarring in children with acute pyelonephritis","volume":"28","author":"Sobouti","year":"2013","journal-title":"Pediatr. Nephrol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1016\/S0022-5347(05)69004-0","article-title":"Suppression of renal inflammation with vitamins A and E in ascending pyelonephritis in rats","volume":"161","author":"Bennett","year":"1999","journal-title":"J. Urol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s00431-010-1297-1","article-title":"The effect of vitamin A on renal damage following acute pyelonephritis in children","volume":"170","author":"Ayazi","year":"2011","journal-title":"Eur. J. Pediatr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nrmicro3432","article-title":"Urinary tract infections: Epidemiology, mechanisms of infection and treatment options","volume":"13","author":"Walker","year":"2015","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_53","first-page":"2334","article-title":"Effect of avitaminosis A and hypervitaminosis A on urinary bladder carcinogenicity of N-(4-(5-Nitro-2-furyl)-2-thiazolyl)formamide","volume":"36","author":"Cohen","year":"1976","journal-title":"Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1093\/jn\/123.5.823","article-title":"Vitamin A deficiency impairs some aspects of the host response to influenza A virus infection in BALB\/c mice","volume":"123","author":"Stephensen","year":"1993","journal-title":"J. Nutr."},{"key":"ref_55","first-page":"705","article-title":"The combined effects of vitamin A-deficiency and cigarette smoke on rat tracheal epithelium","volume":"68","author":"Shields","year":"1987","journal-title":"Br. J. Exp. Pathol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/intimm\/dxv064","article-title":"Vitamin A deficient mice exhibit increased viral antigens and enhanced cytokine\/chemokine production in nasal tissues following respiratory virus infection despite the presence of FoxP3+ T cells","volume":"28","author":"Penkert","year":"2016","journal-title":"Int. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1093\/jnci\/90.16.1198","article-title":"Histopathologic and molecular alterations in bronchial epithelium in habitual smokers of marijuana, cocaine, and\/or tobacco","volume":"90","author":"Barsky","year":"1998","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_58","first-page":"461","article-title":"Correlation between precancerous bronchial metaplasia and cigarette consumption, and preliminary results of retinoid treatment","volume":"5","author":"Mathe","year":"1982","journal-title":"Cancer Detect. Prev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1378\/chest.103.5.1429","article-title":"Squamous metaplasia of the bronchial mucosa and its relationship to smoking","volume":"103","author":"Peters","year":"1993","journal-title":"Chest"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/sj.onc.1202349","article-title":"Sequential molecular abnormalities are involved in the multistage development of squamous cell lung carcinoma","volume":"18","author":"Wistuba","year":"1999","journal-title":"Oncogene"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/nrc.2017.68","article-title":"Metaplasia: Tissue injury adaptation and a precursor to the dysplasia-cancer sequence","volume":"17","author":"Giroux","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S1040-8428(01)00144-5","article-title":"Retinoids and their receptors in cancer development and chemoprevention","volume":"41","author":"Sun","year":"2002","journal-title":"Crit. Rev. Oncol. Hemat."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/S0140-6736(80)90169-5","article-title":"Low serum-vitamin-A and subsequent risk of cancer. Preliminary results of a prospective study","volume":"2","author":"Wald","year":"1980","journal-title":"Lancet"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1111\/j.1753-4887.1990.tb02936.x","article-title":"Vitamin A and lung cancer","volume":"48","author":"Willett","year":"1990","journal-title":"Nutr. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3389\/fonc.2017.00023","article-title":"Inverse Association between Dietary Intake of Selected Carotenoids and Vitamin C and Risk of Lung Cancer","volume":"7","author":"Shareck","year":"2017","journal-title":"Front. Oncol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"9309","DOI":"10.3390\/nu7115463","article-title":"Association of Dietary Vitamin A and beta-Carotene Intake with the Risk of Lung Cancer: A Meta-Analysis of 19 Publications","volume":"7","author":"Yu","year":"2015","journal-title":"Nutrients"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1111\/j.1365-4632.2007.03425.x","article-title":"Chemotherapeutic\/chemopreventive role of retinoids in chemically induced skin carcinogenesis in albino mice","volume":"46","author":"Bukhari","year":"2007","journal-title":"Int. J. Dermatol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1038\/sj.bjc.6604320","article-title":"The rexinoid, bexarotene, prevents the development of premalignant lesions in MMTV-erbB2 mice","volume":"98","author":"Li","year":"2008","journal-title":"Br. J. Cancer"},{"key":"ref_69","first-page":"5","article-title":"Chemoprevention of OH-BBN-induced bladder cancer in mice by oltipraz, alone and in combination with 4-HPR and DFMO","volume":"14","author":"Moon","year":"1994","journal-title":"Anticancer Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1093\/annonc\/mdm195","article-title":"Antitumor activity of the combination of synthetic retinoid ST1926 and cisplatin in ovarian carcinoma models","volume":"18","author":"Pisano","year":"2007","journal-title":"Ann. Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1097\/00005537-200107000-00013","article-title":"Pulsed-dye laser and retinoic acid delay progression of oral squamous cell carcinoma: A murine model","volume":"111","author":"Shah","year":"2001","journal-title":"Laryngoscope"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1158\/1940-6207.CAPR-09-0221","article-title":"Preventive effects of bexarotene and budesonide in a genetically engineered mouse model of small cell lung cancer","volume":"2","author":"Wang","year":"2009","journal-title":"Cancer Prev. Res. (Phila.)"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"5774","DOI":"10.1200\/JCO.2005.14.373","article-title":"Phase II trial of the novel retinoid, bexarotene, and gemcitabine plus carboplatin in advanced non-small-cell lung cancer","volume":"23","author":"Edelman","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1007\/s00277-016-2754-3","article-title":"Successful treatment of acute promyelocytic leukemia with arsenic trioxide and all-trans retinoic acid in a double lung and kidney transplanted patient","volume":"95","author":"Peterlin","year":"2016","journal-title":"Ann. Hematol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.3892\/or_00000317","article-title":"Beta-interferon, retinoids and ta\/moxifen in metastatic breast cancer: Long-term follow-up of a phase II study","volume":"21","author":"Recchia","year":"2009","journal-title":"Oncol. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1158\/1055-9965.EPI-06-0183","article-title":"A phase I-II preoperative biomarker trial of fenretinide in ascitic ovarian cancer","volume":"15","author":"Colombo","year":"2006","journal-title":"Cancer Epidemiol. Biomark."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group (1994). The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N. Engl. J. Med., 330, 1029\u20131035.","DOI":"10.1056\/NEJM199404143301501"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/0196-0709(93)90014-X","article-title":"The EUROSCAN study: A progress report","volume":"14","author":"Pastorino","year":"1993","journal-title":"Am. J. Otolaryngol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1056\/NEJM199605023341801","article-title":"Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease","volume":"334","author":"Hennekens","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1097\/01.cej.0000215612.98132.18","article-title":"Chemoprevention of lung cancers: Lessons from CARET, the beta-carotene and retinol efficacy trial, and prospects for the future","volume":"16","author":"Omenn","year":"2007","journal-title":"Eur. J. Cancer Prev."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1093\/aje\/kwn409","article-title":"Long-term use of beta-carotene, retinol, lycopene, and lutein supplements and lung cancer risk: Results from the VITamins And Lifestyle (VITAL) study","volume":"169","author":"Satia","year":"2009","journal-title":"Am. J. Epidemiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1056\/NEJM199605023341802","article-title":"Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease","volume":"334","author":"Omenn","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1093\/jnci\/djs195","article-title":"Dietary supplements and cancer prevention: Balancing potential benefits against proven harms","volume":"104","author":"Martinez","year":"2012","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1002\/ijc.25008","article-title":"Beta-carotene supplementation and cancer risk: A systematic review and metaanalysis of randomized controlled trials","volume":"127","author":"Norat","year":"2010","journal-title":"Int. J. Cancer"},{"key":"ref_85","first-page":"350","article-title":"Fruits and vegetables are associated with lower lung cancer risk only in the placebo arm of the beta-carotene and retinol efficacy trial (CARET)","volume":"12","author":"Neuhouser","year":"2003","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"262S","DOI":"10.1093\/jn\/134.1.262S","article-title":"The enigma of beta-carotene in carcinogenesis: What can be learned from animal studies","volume":"134","author":"Russell","year":"2004","journal-title":"J. Nutr."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"560","DOI":"10.4049\/jimmunol.146.2.560","article-title":"IL-1 alpha is produced by T lymphocytes activated via the CD2 plus CD28 pathways","volume":"146","author":"Cerdan","year":"1991","journal-title":"J. Immunol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"8151","DOI":"10.1128\/JVI.00496-06","article-title":"Role of CCL5 (RANTES) in viral lung disease","volume":"80","author":"Culley","year":"2006","journal-title":"J. Virol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s40463-016-0183-x","article-title":"Differences in RANTES and IL-6 levels among chronic rhinosinusitis patients with predominant gram-negative and gram-positive infection","volume":"46","author":"Rammal","year":"2017","journal-title":"J. Otolaryngol. Head Neck Surg."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1128\/CVI.05576-11","article-title":"Reduced frequencies and heightened CD103 expression among virus-induced CD8(+) T cells in the respiratory tract airways of vitamin A-deficient mice","volume":"19","author":"Rudraraju","year":"2012","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Crawford, A., Angelosanto, J.M., Nadwodny, K.L., Blackburn, S.D., and Wherry, E.J. (2011). A role for the chemokine RANTES in regulating CD8 T cell responses during chronic viral infection. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002098"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1128\/CVI.00757-13","article-title":"Intranasal administration of retinyl palmitate with a respiratory virus vaccine corrects impaired mucosal IgA response in the vitamin A-deficient host","volume":"21","author":"Surman","year":"2014","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1016\/j.vaccine.2014.03.025","article-title":"Oral retinyl palmitate or retinoic acid corrects mucosal IgA responses toward an intranasal influenza virus vaccine in vitamin A deficient mice","volume":"32","author":"Surman","year":"2014","journal-title":"Vaccine"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1128\/CVI.00739-15","article-title":"Vitamin supplementation at the time of immunization with cold-adapted influenza virus vaccine corrects poor antibody responses in mice deficient for vitamins A and D","volume":"23","author":"Surman","year":"2016","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1089\/vim.2012.0023","article-title":"Vitamin A deficiency disrupts vaccine-induced antibody-forming cells and the balance of IgA\/IgG isotypes in the upper and lower respiratory tract","volume":"25","author":"Surman","year":"2012","journal-title":"Viral Immunol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.imlet.2019.05.011","article-title":"Background check: Profound differences in serum antibody isotypes among C57BL\/6 mouse substrains discourage substrain interchanges in immunology experiments","volume":"216","author":"Jones","year":"2019","journal-title":"Immunol. Lett."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"103996","DOI":"10.1016\/j.cellimm.2019.103996","article-title":"Matters of life and death: How estrogen and estrogen receptor binding to the immunoglobulin heavy chain locus may influence outcomes of infection, allergy, and autoimmune disease","volume":"346","author":"Jones","year":"2019","journal-title":"Cell. Immunol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1089\/vim.2019.0144","article-title":"From Influenza Virus Infections to Lupus: Synchronous Estrogen Receptor alpha and RNA Polymerase II Binding Within the Immunoglobulin Heavy Chain Locus","volume":"33","author":"Jones","year":"2020","journal-title":"Viral Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Patel, N., Penkert, R.R., Jones, B.G., Sealy, R.E., Surman, S.L., Sun, Y., Tang, L., DeBeauchamp, J., Webb, A., and Richardson, J. (2019). Baseline Serum Vitamin A and D Levels Determine Benefit of Oral Vitamin A&D Supplements to Humoral Immune Responses Following Pediatric Influenza Vaccination. Viruses, 11.","DOI":"10.3390\/v11100907"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1097\/00006454-199609000-00008","article-title":"Vitamin A therapy for children with respiratory syncytial virus infection: A multicenter trial in the United States","volume":"15","author":"Bresee","year":"1996","journal-title":"Pediatr. Infect. Dis. J."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/15\/5570\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:54:10Z","timestamp":1760176450000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/15\/5570"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,4]]},"references-count":100,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["ijms21155570"],"URL":"https:\/\/doi.org\/10.3390\/ijms21155570","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,4]]}}}