تاثیر ویتامین E بر سیستم ایمنی

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Vitamin E is a fat-soluble antioxidant that can protect the polyunsaturated fatty acids (PUFAs) in the membrane from oxidation, regulate the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), and modulate signal transduction. With advances in understating of the development, function, and regulation of dendritic cells (DCs), macrophages, natural killer (NK) cells, T cells, and B cells, recent studies have focused on vitamin E’s effects on specific immune cells. The Role of Vitamin E in Immunity Ga Young Lee 1,2 and Sung Nim Han 

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DEFINITION AND STRUCTURE Vitamin E is the collective term for four tocopherols (a-, B-, y-, and 6-tocopherols) and four tocotrienols (a-, B-, y-, and 6- tocotrienols) found in food. These forms have antioxidant activities, but cannot be interconverted, and only a- tocopherol meets the human vitamin E requirement. Traber M.G. Vitamin E regulatory mechanisms. Annu. Rev. Nutr. 2007;27:347-362. doi: 10.1146/annurev.nutr.27.061406.093819. [PubMed] [CrossRef] [Google Scholar] 

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SOURCES The major dietary sources of vitamin E are vegetable oils. Nuts are good sources of vitamin E as well . Soybean, sunflower, corn, walnut, cottonseed, palm, and wheat germ oils contain relatively higher amounts of vitamin E than other oils. Safflower and sunflower oils are high in a-tocopherol, soybean and corn oils contain mainly y- tocopherol, and cottonseed oil contains similar proportions of a- and y-tocopherols. Therefore, the types of oils consumed through the diet affect the dietary intake levels of a-tocopherol. Vitamin E supplements are quite popular and Either natural or synthetic forms of a-tocopherol are used as supplements. Sheppard A,J., Pennington J.A.T., Weihrauch J.L. Analysis and distribution of vitamin E in vegetable oils and foods. In: Packer L., Fuchs J., editors. Vitamin E in Health and Disease. Marcel Dekker; New York, NY, USA: 1980. pp. 7-65. [Google Scholar] 

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SOURCES Despite the relatively higher intake of y-tocopherol from the diet than a-tocopherol, a-tocopherol is the major form of vitamin E in the circulation because a- tocopherol transfer protein (a-TTP) has the preferential binding affinity for a-tocopherol. a-TTP is involved in the transfer of a-tocopherol to the plasma membrane. Traber M.G. Vitamin E regulatory mechanisms. Annu. Rev. Nutr. 2007;27:347- 362. doi: 10.1146/annurev.nutr.27.061406.093819. [PubMed] [CrossRef] [Google Scholar] 

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FUNCTION In the presence of vitamin E, peroxyl radicals react with a- tocopherol instead of lipid hydroperoxide, the chain reaction of peroxyl! radical production is stopped, and further oxidation of PUFAs in the membrane is prevented. Tocopheroxy! radicals—produced from a-tocopherol and peroxyl radicals—are reduced by vitamin C or glutathione, form tocopherol dimers, undergo further oxidation, or act as prooxidants. Traber M.G. Vitamin E regulatory mechanisms. Annu. Rev. Nutr. 2007;27:347-362. doi: 10.1146/annurev.nutr.27.061406.093819. [PubMed] [CrossRef] [Google Scholar] 

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FUNCTION The antioxidant activity of vitamin E may be responsible for the regulation of several enzymes involved in signal transduction because the activity of signaling enzymes is regulated by the redox state. The inhibition of PKC by vitamin E has been reported in various cells, and consequently, the inhibition of platelet aggregation; reduced proliferation of monocytes, macrophages, neutrophils, and vascular smooth muscle cells; and decreased superoxide production in neutrophils and macrophages have been observed. Traber M.G., Atkinson J. Vitamin E, antioxidant and nothing m more. Free Rad. Biol. Med. 2007;43:4- 15. doi: 10.1016/j.freeradbiomed.2007.03.024. [PMC free article] [PubMed] [CrossRef] [Google Scholar] Zingg J.M. Vitamin E: A role in signal transduction. Annu. Rev. Nutr. 2015;35:135-173. doi: 10.1146/annurev-nutr-071714-034347. [PubMed] [CrossRef] [Google Scholar] 

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IMMUNE RESPONSES IN HUMANS In humans, many intervention studies have reported increased lymphocyte proliferation in response to mitogenic stimulation, enhanced delayed type hypersensitivity (DTH) response, increased IL-2 production, and decreased IL-6 production with vitamin E supplementation above the recommended levels. The Role of Vitamin E in Immunity Ga Young Lee 1,2 and Sung Nim Han 

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INFECTIOUS DISEASES IN HUMANS In humans, the effects of vitamin E on the natural incidence of infectious diseases have been determined in several studies. Many studies provided evidence that the immunostimulatory effects of vitamin E confer improved resistance to infections. The Role of Vitamin E in Immunity Ga Young Lee 1,2 and Sung Nim Han 

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VITAMIN E AND IMMUNE CELLS The Role of Vitamin E in Immunity Ga Young Lee 1,2 and Sung Nim Han 

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MACROPHAGES Macrophages, important effector cells in the innate immune response, serve as antigen presenting cells (APC) and regulate NK cells and T cells by producing cytokines, reactive oxygen species (ROS), reactive nitrogen species (RNS), and prostaglandins. Cytokines produced by T cells and other immune cells can shift the macrophages into different populations with distinct physiologies. Mosser D.M., Edwards J.P. Exploring the full spectrum of macrophage activation. Nat. Rev. Immunol. 2008;8:958-969. doi: 10.1038/nri2448. [PMC free article] [PubMed] [CrossRef] [Google Scholar] 61. Meydani S.N., Han S.N., Wu D. Vitamin E and immune response in the aged: Molecular mechanisms and clinical implications. Immunol. Rev. 2005;205:269-284. doi: 10.1111/j.0105-2896.2005.00274.x. [PubMed] [CrossRef] [Google Scholar] 

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MACROPHAGES The effects of vitamin E on prostaglandin (PG)E2 production by macrophages from the aged have been suggested as one of the mechanisms by which vitamin E improves the age-associated decrease in the T cell- mediated immune response. Meydani S.N., Han S.N., Wu D. Vitamin E and immune response in the aged: Molecular mechanisms and clinical implications. Immunol. Rev. 2005;205:269-284. doi: 10.1111/j.0105-2896.2005.00274.x. [PubMed] [CrossRef] [Google Scholar] 

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MACROPHAGES In vivo supplementation of vitamin E in allergic asthmatic patients prevented the suppression of alveolar macrophage nuclear factor (erythroid-derived 2)-like 2 (NRF2) activity after allergen challenge. This study presented the possibility of vitamin E’s protective role in allergies and asthmas through regulation of macrophage NRF2 activity, but, further studies are needed to confirm the findings because of the small number of patients and the lack of appropriate controls. Dworski R., Han W., Blackwell T.S., Hoskins A., Freeman M.L. Vitamin E prevents NRF2 suppression by allergens in asthmatic alveolar macrophages in vivo. Free Radic. Biol. Med. 2011;51:516-521. doi: 10.1016/j.freeradbiomed.2011.04.040. [PMC free article] [PubMed] [CrossRef] [Google Scholar] 

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© NATURAL KILLER CELLS NK activity seems to be related with vitamin E status. The NK activity of a boy with Shwachman syndrome who had a severe vitamin E deficiency was low ,but improved after eight weeks of 100 mg/d a-tocopherol supplementation. two-week supplementation of 750 mg vitamin E in colorectal cancer patients resulted in increased NK activity in six out of seven patients. Adachi N., Migita M., Ohta T., Higashi A., Matsuda |. Depressed natural killer cell activity due to decreased natural killer cell population in a vitamin E-deficient patient with Shwachman syndrome: Reversible natural killer cell abnormality by alpha-tocopherol supplementation. Eur. J. Pediatr. 1997;156:444-448. doi: 10.1007/s004310050634. [PubMed] [CrossRef] [Google Scholar] [Ref list] 

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© NATURAL KILLER CELLS Vitamin E treatment did not result in changes in perforin expression or IFN-y production; therefore, mechanisms of improved NK activity by vitamin E could not be determined from the study. Vitamin E ie fate GHA @ Hanson M.G., Ozenci V., Carlsten M.C., Glimelius B.L., Frédin J.E., Masucci G., Malmberg K.J., Kiessling R.V. A short-term dietary supplementation with high doses of vitamin E increases NK cell cytolytic activity in advanced colorectal cancer patients. Cancer Immunol. Immunother. 2007;56:973- 984. doi: 10.1007/s00262-006-0261-4. [PubMed] [CrossRef] [Google Scholar] [Ref list] 

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© DENDRITIC CELLS Dendritic cells (DCs) are effective antigen-presenting cells that recognize pathogens and present pathogen-derived antigens to T cells. The interaction of DCs with pathogen- associated molecular patterns (PAMPs) or damage- associated molecular patterns (DAMPs) elicits the activation and maturation of DCs. DCs are also involved in tolerance and autoimmunity. Several studies have shown that vitamin E could regulate the maturation and functions of DCs. Ganguly D., Haak S., Sisirak V., Reizis B. The role of dendritic cells in autoimmunity. Nat. Rev. Immunol. 2013;13:566-577. doi: 10.1038/nri3477. [PMC free article] [PubMed] [CrossRef] [Google Scholar] Alloatti A., Kotsias ‏رع‎ Magalhaes J.G., Amigorena S. Dendritic cell maturation and cross-presentation: Timing matters! Immunol. Rev. 2016;272:97-108. doi: 10.1111/imr.12432. [PubMed] [CrossRef] {Google Scholar] 

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DENDRITIC CELLS Maternal supplementation with a-tocopherol was effective in decreasing allergic responses in offspring from allergic mothers by affecting the development of subsets of DCs that are critical for allergic responses. y-tocopherol supplementation exerted an opposite response in the same model. In vivo supplementation of y-tocopherol at 250 mg/kg diet in allergic female mice resulted in a higher number of lung eosinophils, a higher number of lung CD11c+ CD11b+ DCs, and higher levels of lung lavage CCL11 in the offspring. Abdala-Valencia H., Soveg F., Cook-Mills J.M. y-Tocopherol supplementation of allergic female mice augments development of CD11¢-+CD11b+ dendritic cells in utero and allergic inflammation in neonates. Am. J. Physiol. Lung Cell. Mol. Physiol. 2016;310:L759-L771. doi: 10.1152/ajplung.00301.2015. [PMC free article] [PubMed] [CrossRef] [Google Scholar] 

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DENDRITIC CELLS Modulation of the immune response by vitamin E has been observed in animal and human studies, and DCs play a critical role in bridging innate and adaptive immune systems and initiating adaptive immune responses. Despite the importance of DCs’ role in adaptive immune responses and in diseases such as autoimmune diseases, few studies have investigated the DC-specific effect of vitamin E. The Role of Vitamin E in Immunity Ga Young Lee 1,2 and Sung Nim Han 

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© T- CELLS The effects of vitamin E on immune cells have been studied the most with T cells. The dysregulation of immune function occurs with aging and the most significant changes are observed in T cells. Age- associated changes in T cells include: (1) defects in T cell receptor (TCR)signal transduction (2) decreased intracellular influx of calcium following stimulation, (3) diminished synapse formation, (4) diminished activation of the mitogen activated protein kinase (MAP kinase) pathway, (5) decreased nuclear factor of activated T-cells(NFAT)binding activity ,and(6)a shift of the T cell population toward memory T cells. The Role of Vitamin E in Immunity Ga Young Lee 1,2 and Sung Nim Han Molano, A.; Meydani, S.N. Vitamin E, signalosomes and gene expression in T cells. Mol. Aspects. Med. 2012, 33, 55-62 

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TeGBLES Vitamin E seems to modulate Th1 and Th2 responses and has implications for the protection against different pathogens (intracellular vs. extracellular pathogens) and the development of different types of chronic diseases (inflammatory vs. allergic diseases). Vitamin E can also affect activation-induced cell death in T cells. The Role of Vitamin E in Immunity Ga Young Lee 1,2 and Sung Nim Han 

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B:CELLS Vitamin E supplementation has been reported to enhance humoral responses. Higher antibody responses have been observed in animals and humans. However, it is hard to differentiate whether vitamin E’s direct effect on B cells or indirect effect through T cells contributes to higher antibody responses. Beharka A.A., Han S.N., Adolfsson O., Wu D., Lipman R., Smith D., Cao G., Meydani M,, Meydani S.N. Long- term dietary antioxidant supplementation reduces production of selected inflammatory mediators by murine macrophages. Nutr. Res. 2000;20:281-296. doi: 10.1016/S0271-5317(99)00160-8. [CrossRef] [Google Scholar] Meydani S.N., Meydani M., Blumberg J.B., Leka L.S., Siber G., Loszewski R., Thompson C., Pedrosa M.C., Diamond R.D., Stollar B.D. Vitamin E supplementation and in vivo immune response in healthy elderly subjects. A randomized controlled trial. JAMA. 1997;277:1380-1386. doi: 10.1001/jama.1997.03540410058031. [PubMed] [CrossRef] [Google Scholar] 

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CONCLUSIONS Vitamin E has been shown to enhance immune responses in animal and human models and to confer protection against several infectious diseases. Suggested mechanisms involved with these changes are: 1. the reduction of PGE2 production by the inhibition of COX2 activity mediated through decreasing NO production The Role of Vitamin E in Immunity Ga Young Lee 1,2 and Sung Nim Han 

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2. the improvement of effective immune synapse formation in naive T cells and the initiation of T cell activation signals. 3. the modulation of Th1/Th2 balance. Higher NK activity and changes in dendritic function such as lower IL-12 production and migration were observed with vitamin E The Role of Vitamin E in Immunity Ga Young Lee 1,2 and Sung Nim Han 

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Different forms of vitamin E exert differential effects on immune cells. Cell-specific effects of vitamin E provide valuable evidence regarding the immunomodulatory mechanisms of vitamin E, but the interplay between immune cells should not be ignored, because interactions between immune cells are critical in the regulation of immune function. The Role of Vitamin E in Immunity Ga Young Lee 1,2 and Sung Nim Han 

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Thanks For your attention