HOW VITAMIN D AFFECTS THE IMMUNE SYSTEM: A REVIEW OF THE LITERATURE
Abstract
Vitamin D is essential for the proper functioning of the immune system, modulating the immune response through the activation of vitamin D receptors (VDR) in various immune cells. Vitamin D plays a crucial role in protecting against infections, particularly respiratory infections, and its deficiency is associated with an increased risk of autoimmune diseases. Although the results of studies on vitamin D supplementation in the treatment of autoimmune diseases are mixed, there is growing interest in its potential impact on the course of these diseases. This review discusses the mechanisms of vitamin D action in the context of the immune system and its significance in preventing infections and autoimmune diseases. Research indicates the need for further analysis to establish optimal supplementation doses of vitamin D and its effectiveness in different patient groups.
References
Naeem Z. Vitamin d deficiency- an ignored epidemic. Int J Health Sci (Qassim). 2010 Jan;4(1):V-VI. PMID: 21475519; PMCID: PMC3068797.
Holick MF. Vitamin D: a D-Lightful health perspective. Nutr Rev. 2008 Oct;66(10 Suppl 2):S182-94. doi: 10.1111/j.1753-4887.2008.00104.x. PMID: 18844847.
Aranow C. Vitamin D and the immune system. J Investig Med. 2011 Aug;59(6):881-6. doi: 10.2310/JIM.0b013e31821b8755. PMID: 21527855; PMCID: PMC3166406.
DeLuca HF. Vitamin D: Historical Overview. Vitam Horm. 2016;100:1-20. doi: 10.1016/bs.vh.2015.11.001. Epub 2015 Dec 19. PMID: 26827946.
Holick MF. Vitamin D deficiency. N Engl J Med. 2007 Jul 19;357(3):266-81. doi: 10.1056/NEJMra070553. PMID: 17634462.
Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G. Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects. Physiol Rev. 2016 Jan;96(1):365-408. doi: 10.1152/physrev.00014.2015. PMID: 26681795; PMCID: PMC4839493.
Wacker M, Holick MF. Sunlight and Vitamin D: A global perspective for health. Dermatoendocrinol. 2013 Jan 1;5(1):51-108. doi: 10.4161/derm.24494. PMID: 24494042; PMCID: PMC3897598.
Bouillon R, Marcocci C, Carmeliet G, Bikle D, White JH, Dawson-Hughes B, Lips P, Munns CF, Lazaretti-Castro M, Giustina A, Bilezikian J. Skeletal and Extraskeletal Actions of Vitamin D: Current Evidence and Outstanding Questions. Endocr Rev. 2019 Aug 1;40(4):1109-1151. doi: 10.1210/er.2018-00126. PMID: 30321335; PMCID: PMC6626501.
Jones G. Pharmacokinetics of vitamin D toxicity. Am J Clin Nutr. 2008 Aug;88(2):582S-586S. doi: 10.1093/ajcn/88.2.582S. PMID: 18689406.
Daryabor G, Gholijani N, Kahmini FR. A review of the critical role of vitamin D axis on the immune system. Exp Mol Pathol. 2023 Aug;132-133:104866. doi: 10.1016/j.yexmp.2023.104866. Epub 2023 Aug 17. PMID: 37572961.
Kongsbak M, Levring TB, Geisler C, von Essen MR. The vitamin d receptor and T cell function. Front Immunol. 2013 Jun 18;4:148. doi: 10.3389/fimmu.2013.00148. PMID: 23785369; PMCID: PMC3684798..
Sîrbe C, Rednic S, Grama A, Pop TL. An Update on the Effects of Vitamin D on the Immune System and Autoimmune Diseases. Int J Mol Sci. 2022 Aug 29;23(17):9784. doi: 10.3390/ijms23179784. PMID: 36077185; PMCID: PMC9456003.
Crane-Godreau MA, Clem KJ, Payne P, Fiering S. Vitamin D Deficiency and Air Pollution Exacerbate COVID-19 Through Suppression of Antiviral Peptide LL37. Front Public Health. 2020 May 28;8:232. doi: 10.3389/fpubh.2020.00232. PMID: 32671009; PMCID: PMC7326088.
Ramos-Martínez E, López-Vancell MR, Fernández de Córdova-Aguirre JC, Rojas-Serrano J, Chavarría A, Velasco-Medina A, Velázquez-Sámano G. Reduction of respiratory infections in asthma patients supplemented with vitamin D is related to increased serum IL-10 and IFNγ levels and cathelicidin expression. Cytokine. 2018 Aug;108:239-246. doi: 10.1016/j.cyto.2018.01.001. Epub 2018 May 7. PMID: 29402723.
Zhang Y, Leung DY, Richers BN, Liu Y, Remigio LK, Riches DW, Goleva E. Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. J Immunol. 2012 Mar 1;188(5):2127-35. doi: 10.4049/jimmunol.1102412. Epub 2012 Feb 1. PMID: 22301548; PMCID: PMC3368346.
Almerighi C, Sinistro A, Cavazza A, Ciaprini C, Rocchi G, Bergamini A. 1Alpha,25-dihydroxyvitamin D3 inhibits CD40L-induced pro-inflammatory and immunomodulatory activity in human monocytes. Cytokine. 2009 Mar;45(3):190-7. doi: 10.1016/j.cyto.2008.12.009. Epub 2009 Jan 30. PMID: 19186073.
Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, Dubnov-Raz G, Esposito S, Ganmaa D, Ginde AA, Goodall EC, Grant CC, Griffiths CJ, Janssens W, Laaksi I, Manaseki-Holland S, Mauger D, Murdoch DR, Neale R, Rees JR, Simpson S Jr, Stelmach I, Kumar GT, Urashima M, Camargo CA Jr. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017 Feb 15;356:i6583. doi: 10.1136/bmj.i6583. PMID: 28202713; PMCID: PMC5310969.
Jolliffe DA, Griffiths CJ, Martineau AR. Vitamin D in the prevention of acute respiratory infection: systematic review of clinical studies. J Steroid Biochem Mol Biol. 2013 Jul;136:321-9. doi: 10.1016/j.jsbmb.2012.11.017. Epub 2012 Dec 7. PMID: 23220552.
Murai IH, Fernandes AL, Sales LP, Pinto AJ, Goessler KF, Duran CSC, Silva CBR, Franco AS, Macedo MB, Dalmolin HHH, Baggio J, Balbi GGM, Reis BZ, Antonangelo L, Caparbo VF, Gualano B, Pereira RMR. Effect of a Single High Dose of Vitamin D3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19: A Randomized Clinical Trial. JAMA. 2021 Mar 16;325(11):1053-1060. doi: 10.1001/jama.2020.26848. PMID: 33595634; PMCID: PMC7890452.
Lanham-New SA, Webb AR, Cashman KD, Buttriss JL, Fallowfield JL, Masud T, Hewison M, Mathers JC, Kiely M, Welch AA, Ward KA, Magee P, Darling AL, Hill TR, Greig C, Smith CP, Murphy R, Leyland S, Bouillon R, Ray S, Kohlmeier M. Vitamin D and SARS-CoV-2 virus/COVID-19 disease. BMJ Nutr Prev Health. 2020 May 13;3(1):106-110. doi: 10.1136/bmjnph-2020-000089. PMID: 33230499; PMCID: PMC7246103.
Maruotti N, Cantatore FP. Vitamin D and the immune system. J Rheumatol. 2010 Mar;37(3):491-5. doi: 10.3899/jrheum.090797. Epub 2010 Jan 15. PMID: 20080911.
Jagannath VA, Filippini G, Di Pietrantonj C, Asokan GV, Robak EW, Whamond L, Robinson SA. Vitamin D for the management of multiple sclerosis. Cochrane Database Syst Rev. 2018 Sep 24;9(9):CD008422. doi: 10.1002/14651858.CD008422.pub3. PMID: 30246874; PMCID: PMC6513642.
Prietl B, Treiber G, Pieber TR, Amrein K. Vitamin D and immune function. Nutrients. 2013 Jul 5;5(7):2502-21. doi: 10.3390/nu5072502. PMID: 23857223; PMCID: PMC3738984.
Guan Y, Hao Y, Guan Y, Bu H, Wang H. The Effect of Vitamin D Supplementation on Rheumatoid Arthritis Patients: A Systematic Review and Meta-Analysis. Front Med (Lausanne). 2020 Oct 30;7:596007. doi: 10.3389/fmed.2020.596007. PMID: 33195358; PMCID: PMC7661491.
Bellan M, Andreoli L, Nerviani A, Piantoni S, Avanzi GC, Soddu D, Hayden E, Pirisi M, Sainaghi PP. Is cholecalciferol a potential disease-modifying anti-rheumatic drug for the management of rheumatoid arthritis? Clin Exp Rheumatol. 2020 Mar-Apr;38(2):343-349. doi: 10.55563/clinexprheumatol/tdf172. Epub 2019 Sep 17. PMID: 31573472.
Brożyna AA, Slominski RM, Nedoszytko B, Zmijewski MA, Slominski AT. Vitamin D Signaling in Psoriasis: Pathogenesis and Therapy. Int J Mol Sci. 2022 Aug 2;23(15):8575. doi: 10.3390/ijms23158575. PMID: 35955731; PMCID: PMC9369120.
Amital H, Szekanecz Z, Szücs G, Dankó K, Nagy E, Csépány T, Kiss E, Rovensky J, Tuchynova A, Kozakova D, Doria A, Corocher N, Agmon-Levin N, Barak V, Orbach H, Zandman-Goddard G, Shoenfeld Y. Serum concentrations of 25-OH vitamin D in patients with systemic lupus erythematosus (SLE) are inversely related to disease activity: is it time to routinely supplement patients with SLE with vitamin D? Ann Rheum Dis. 2010 Jun;69(6):1155-7. doi: 10.1136/ard.2009.120329. Epub 2010 May 3. PMID: 20439290.
Gubatan J, Mitsuhashi S, Zenlea T, Rosenberg L, Robson S, Moss AC. Low Serum Vitamin D During Remission Increases Risk of Clinical Relapse in Patients With Ulcerative Colitis. Clin Gastroenterol Hepatol. 2017 Feb;15(2):240-246.e1. doi: 10.1016/j.cgh.2016.05.035. Epub 2016 Jun 4. PMID: 27266980; PMCID: PMC5136522.
Holick MF. Vitamin D: evolutionary, physiological and health perspectives. Curr Drug Targets. 2011 Jan;12(1):4-18. doi: 10.2174/138945011793591635. PMID: 20795941.
Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium. Dietary Reference Intakes for Calcium and Vitamin D. Ross AC, Taylor CL, Yaktine AL, Del Valle HB, editors. Washington (DC): National Academies Press (US); 2011. PMID: 21796828.
Jolliffe DA, Camargo CA Jr, Sluyter JD, Aglipay M, Aloia JF, Ganmaa D, Bergman P, Bischoff-Ferrari HA, Borzutzky A, Damsgaard CT, Dubnov-Raz G, Esposito S, Gilham C, Ginde AA, Golan-Tripto I, Goodall EC, Grant CC, Griffiths CJ, Hibbs AM, Janssens W, Khadilkar AV, Laaksi I, Lee MT, Loeb M, Maguire JL, Majak P, Mauger DT, Manaseki-Holland S, Murdoch DR, Nakashima A, Neale RE, Pham H, Rake C, Rees JR, Rosendahl J, Scragg R, Shah D, Shimizu Y, Simpson-Yap S, Trilok-Kumar G, Urashima M, Martineau AR. Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials. Lancet Diabetes Endocrinol. 2021 May;9(5):276-292. doi: 10.1016/S2213-8587(21)00051-6. Epub 2021 Mar 30. PMID: 33798465.
Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006 Dec 20;296(23):2832-8. doi: 10.1001/jama.296.23.2832. PMID: 17179460.
Views:
13
Downloads:
9
Copyright (c) 2025 Sandra Khiralla-Gawlik, Konrad Strużek, Agnieszka Kwiatkowska, Ewelina Mączka, Wiktor Tracz, Patrycja Świercz, Kinga Teper, Aleksandra Anna Strzelecka, Aleksandra Ewa Basak

This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.