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Vitamin A and retinoic acid in T cell-related immunity
Open accessAbstract
Interest in vitamin A as a regulator of immune function goes back to the early 1900s. Recently, several lines of evidence have converged to show that retinoic acid (RA), a major oxidative metabolite of vitamin A, plays a key role in the differentiation of T cell subsets, the migration of T cells into tissues, and the proper development of T cell-dependent antibody responses. This review discusses evidence from experimental studies that RA promotes the differentiation of regulatory T cells, which help to suppress inflammatory reactions, and plays a significant role in normal mucosal immunity by modulating T cell activation and regulating cell trafficking. RA also promotes antibody responses to T cell-dependent antigens. Conversely, in a state of vitamin A deficiency, inflammatory T cell reactions may be inadequately opposed and therefore become dominant. Although data from human studies are still needed, the framework now developed from studies in mice and rat models suggests that adequate vitamin A status, whether derived from ingestion of preformed retinol or β-carotene, is important for maintaining a proper balance of well-regulated T cell functions and for preventing excessive or prolonged inflammatory reactions.
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“In the presence of vitamin A, IL-2 levels are increased, which stimulates the differentiation of T cells into regulatory T cells, which are important mediators for the prevention of autoimmune responses [129,208].”
From Vitamin A Update: Forms, Sources, Kinetics, Detection, Function, Deficiency, Therapeutic Use and Toxicity (2021) · cites this paper as [208]
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Cites
Mosmann, T. R., & Coffman, R. L. (1989) · Annual Review of Immunology · doi:10.1146/annurev.iy.07.040189.001045 · Cited by 7,692
Mosmann, T. R., Cherwinski, H. M., Bond, M. W., Giedlin, M. A., & Coffman, R. L. (1986) · The Journal of Immunology · doi:10.4049/jimmunol.136.7.2348 · Cited by 7,553
Meijer, L., Nelson, D. J., Riazanski, V., Gabdoulkhakova, A. G., Héry-Arnaud, G., Berre, R. L., Loaëc, N., Oumata, N., Galons, H., Nowak, E., et al. (2016) · Journal of Innate Immunity · doi:10.1159/000444256 · Cited by 5,008
Coombes, J. L., Siddiqui, K. R. R., Arancibia-Cárcamo, C. V., Hall, J. A., Sun, C., Belkaid, Y., & Powrie, F. M. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070590 · Cited by 2,708
FOXP3+ regulatory T cells in the human immune system
Sakaguchi, S., Miyara, M., Costantino, C. M., & Hafler, D. A. (2010) · Nature reviews. Immunology · doi:10.1038/nri2785 · Cited by 2,524
What works? Interventions for maternal and child undernutrition and survival
Bhutta, Z. A., Ahmed, T., Black, R. E., Cousens, S. N., Dewey, K. G., Giugliani, E. R. J., Haider, B. A., Kirkwood, B. R., Morris, S. S., Sachdev, H. S., et al. (2008) · The Lancet · doi:10.1016/s0140-6736(07)61693-6 · Cited by 2,264
Reciprocal T H 17 and Regulatory T Cell Differentiation Mediated by Retinoic Acid
Mucida, D., Park, Y., Kim, G., Turovskaya, O., Scott, I., Kronenberg, M., & Cheroutre, H. (2007) · Science · doi:10.1126/science.1145697 · Cited by 1,982
IL‐6: Regulator of Treg/Th17 balance
Kimura, A., & Kishimoto, T. (2010) · European Journal of Immunology · doi:10.1002/eji.201040391 · Cited by 1,654
Plasticity of CD4+ T Cell Lineage Differentiation
Zhou, L., Chong, M. M. W., & Littman, D. R. (2009) · Immunity · doi:10.1016/j.immuni.2009.05.001 · Cited by 1,551
Retinoic acid imprints gut-homing specificity on T cells
Iwata, M., Hirakiyama, A., Eshima, Y., Kagechika, H., Kato, C., & Song, S.-Y. (2004) · Immunity · doi:10.1016/j.immuni.2004.08.011 · Cited by 1,541
Wei, G., Wei, L., Zhu, J., Zang, C., Hu-Li, J., Yao, Z., Cui, K., Kanno, Y., Roh, T.-Y., Watford, W. T., et al. (2009) · Immunity · doi:10.1016/j.immuni.2008.12.009 · Cited by 1,152
Overview of retinoid metabolism and function
Blomhoff, R., & Blomhoff, H. K. (2006) · Journal of Neurobiology · doi:10.1002/neu.20242 · Cited by 981
Benson, M. J., Pino-Lagos, K., Rosemblatt, M., & Noelle, R. J. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070719 · Cited by 847
A Membrane Receptor for Retinol Binding Protein Mediates Cellular Uptake of Vitamin A
Kawaguchi, R., Yu, J., Honda, J., Hu, J., Whitelegge, J., Ping, P., Wiita, P., Bok, D., & Sun, H. (2007) · Science · doi:10.1126/science.1136244 · Cited by 836
V ITAMIN A, I NFECTION , AND I MMUNE F UNCTION *
Stephensen, C. B. (2001) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.21.1.167 · Cited by 776
Human CD25highFoxp3pos regulatory T cells differentiate into IL-17–producing cells
Koenen, H. J. P. M., Smeets, R. L., Vink, P. M., van Rijssen, E., Boots, A. M. H., & Joosten, I. (2008) · Blood · doi:10.1182/blood-2008-01-133967 · Cited by 756
Epigenetic control of T-helper-cell differentiation
Wilson, C. B., Rowell, E. A., & Sekimata, M. (2009) · Nature reviews. Immunology · doi:10.1038/nri2487 · Cited by 692
Xiao, S., Jin, H., Korn, T., Liu, S. M., Oukka, M., Lim, B., & Kuchroo, V. K. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.4.2277 · Cited by 538
Djuretic, I. M., Levanon, D., Negreanu, V., Groner, Y., Rao, A., & Ansel, K. M. (2006) · Nature Immunology · doi:10.1038/ni1424 · Cited by 532
Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity
Zhou, X., Jeker, L. T., Fife, B. T., Zhu, S., Anderson, M. S., McManus, M. T., & Bluestone, J. A. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20080707 · Cited by 520
Interplay between the TH17 and TReg cell lineages: a (co-)evolutionary perspective
Weaver, C. T., & Hatton, R. D. (2009) · Nature reviews. Immunology · doi:10.1038/nri2660 · Cited by 412
Effects of Vitamin A Supplementation on Immune Responses and Correlation with Clinical Outcomes
Villamor, E., & Fawzi, W. W. (2005) · Clinical Microbiology Reviews · doi:10.1128/cmr.18.3.446-464.2005 · Cited by 405
Expanded Programme on Immunization
Kassianos, G. C. (2001) · doi:10.1002/9780470693841.ch8 · Cited by 397
Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens
DePaolo, R. W., Abadie, V., Tang, F., Fehlner-Peach, H., Hall, J. A., Wang, W., Marietta, E. V., Kasarda, D. D., Waldmann, T. A., Murray, J. A., et al. (2011) · Nature · doi:10.1038/nature09849 · Cited by 389
Iwata, M. (2003) · International Immunology · doi:10.1093/intimm/dxg101 · Cited by 294
VITAMIN A AS AN ANTI-INFECTIVE AGENT
Green, H. N., & Mellanby, E. (1928) · BMJ · doi:10.1136/bmj.2.3537.691 · Cited by 291
Takahashi, H., Kanno, T., Nakayamada, S., Hirahara, K., Sciumè, G., Muljo, S. A., Kuchen, S., Casellas, R. C., Wei, L., Kanno, Y., et al. (2012) · Nature Immunology · doi:10.1038/ni.2286 · Cited by 285
A global clinical view on vitamin A and carotenoids
Sommer, A. H., & Vyas, K. S. (2012) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.112.034868 · Cited by 215
Ziegler, T. R., Evans, M. E., Fernández‐Estívariz, C., & Jones, D. P. (2003) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.23.011702.073036 · Cited by 207
Vitamin A and immunity to viral, bacterial and protozoan infections
Semba, R. D. (1999) · Proceedings of The Nutrition Society · doi:10.1017/s0029665199000944 · Cited by 196
The role of the nuclear hormone receptor RORγt in the development of lymph nodes and Peyer's patches
Eberl, G., & Littman, D. R. (2003) · Immunological Reviews · doi:10.1034/j.1600-065x.2003.00074.x · Cited by 192
Nuclear and cytoplasmic AID in extrafollicular and germinal center B cells
Cattoretti, G., Büttner, M., Shaknovich, R., Kremmer, E., Alobeid, B., & Niedobitek, G. (2006) · Blood · doi:10.1182/blood-2005-10-4170 · Cited by 187
FOXP3 and the regulation of Treg/Th17 differentiation
Ziegler, S. F., & Buckner, J. H. (2009) · Microbes and Infection · doi:10.1016/j.micinf.2009.04.002 · Cited by 177
Molenaar, R., Knippenberg, M., Goverse, G., Olivier, B. J., de Vos, A. F., O’Toole, T. G., & Mebius, R. E. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1001672 · Cited by 168
Impaired Immunity in Vitamin A-Deficient Mice
Smith, S. M., Levy, N. S., & Hayes, C. E. (1987) · Journal of Nutrition · doi:10.1093/jn/117.5.857 · Cited by 156
Vitamin A Enhances in Vitro Th2 Development Via Retinoid X Receptor Pathway
Stephensen, C. B., Rasooly, R., Jiang, X., Ceddia, M. A., Weaver, C. T., Chandraratna, R. A. S., & Bucy, R. P. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.9.4495 · Cited by 153
Takaki, H., Ichiyama, K., Koga, K., Chinen, T., Takaesu, G., Sugiyama, Y., Kato, S., Yoshimura, A., & Kobayashi, T. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m801123200 · Cited by 153
Vitamin A deficiency results in a priming environment conducive for Th1 cell development
Cantorna, M. T., Nashold, F. E., & Hayes, C. E. (1995) · European Journal of Immunology · doi:10.1002/eji.1830250629 · Cited by 145
Vitamin A deficiency in mice causes a systemic expansion of myeloid cells
Kuwata, T., Wang, I., Tamura, T., Ponnamperuma, R. M., Levine, R., Holmes, K. L., Morse, H. C., Luca, L. M. D., & Ozato, K. (2000) · Blood · doi:10.1182/blood.v95.11.3349 · Cited by 141
Eksteen, B., Mora, J. R., Shepherd, E. L., Henderson, N. C., Lee–Turner, L., Villablanca, E. J., Curbishley, S. M., Aspinall, A. I., von Andrian, U. H., & Adams, D. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.02.046 · Cited by 131
Retinoic acid production by intestinal dendritic cells and its role in T-cell trafficking
Iwata, M. (2008) · Seminars in Immunology · doi:10.1016/j.smim.2008.09.002 · Cited by 118
Van, Y.-H., Lee, W.-H., Ortiz, S., Lee, M.-H., Qin, H., & Liu, C. (2008) · Diabetes · doi:10.2337/db08-1154 · Cited by 117
Hoag, K. A., Nashold, F. E., Hayes, C. E., & Goverman, J. M. (2002) · Journal of Nutrition · doi:10.1093/jn/132.12.3736 · Cited by 115
Nine lives: plasticity among T helper cell subsets
Locksley, R. M. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20091442 · Cited by 105
Pasatiempo, A. M. G., Kinoshita, M., Taylor, C. E., & Ross, A. C. (1990) · The FASEB Journal · doi:10.1096/fasebj.4.8.2110538 · Cited by 96
Self-citationMucida, D., Park, Y., & Cheroutre, H. (2008) · Seminars in Immunology · doi:10.1016/j.smim.2008.08.001 · Cited by 96
Kang, S. G., Wang, C., Matsumoto, S., & Kim, C. H. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.06.063 · Cited by 95
Zhao, Z., & Ross, A. C. (1995) · Journal of Nutrition · doi:10.1093/jn/125.8.2064 · Cited by 89
Self-citationRegulation of mucous differentiation and mucin gene expression in the tracheobronchial epithelium
Gray, T. E., Koo, J.-S., & Nettesheim, P. (2001) · Toxicology · doi:10.1016/s0300-483x(00)00455-8 · Cited by 88
Stephensen, C. B., Jiang, X., & Freytag, T. L. (2004) · Journal of Nutrition · doi:10.1093/jn/134.10.2660 · Cited by 84
Vitamin A Deficiency Alters Rat Neutrophil Function ,
Twining, S. S., Schulte, D. P., Wilson, P. M., Fish, B. L., & Moulder, J. E. (1997) · Journal of Nutrition · doi:10.1093/jn/127.4.558 · Cited by 82
Ma, Y., Chen, Q., & Ross, A. C. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.12.7961 · Cited by 76
Self-citationProgress in Reducing Global Measles Deaths, 1999-2004
(2006) · PsycEXTRA Dataset · doi:10.1037/e481842006-008 · Cited by 72
Takeuchi, H., Yokota, A., Ohoka, Y., & Iwata, M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016089 · Cited by 65
Vitamin A as a Regulator of Antigen Presenting Cells ,
Duriancik, D. M., Lackey, D. E., & Hoag, K. A. (2010) · Journal of Nutrition · doi:10.3945/jn.110.124461 · Cited by 65
Vitamin A Supplementation and Child Morbidity and Mortality in Developing Countries
Beaton, G. H., Martorell, R., Aronson, K. A., Edmonston, B., McCabe, G. P., & Harvey, B. J. (1994) · Food and Nutrition Bulletin · doi:10.1177/156482659401500414 · Cited by 63
Regulation of B cell proliferation and differentiation by retinoic acid
Ertesvåg, Å., Naderi, S., & Blomhoff, H. K. (2008) · Seminars in Immunology · doi:10.1016/j.smim.2008.06.005 · Cited by 60
Intestinal perfusion of β -carotene in the ferret raises retinoic acid level in portal blood
Wang, X., Russell, R. M., Marini, R. P., Tang, G., Dolnikowski, G. G., Fox, J. G., & Krinsky, N. I. (1993) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(93)90157-5 · Cited by 57
Stephensen, C. B., Moldoveanu, Z., & Gangopadhyay, N. N. (1996) · Journal of Nutrition · doi:10.1093/jn/126.1.94 · Cited by 54
Ma, Y., & Ross, A. C. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506438102 · Cited by 54
Self-citationChen, Q., & Ross, A. C. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0505018102 · Cited by 51
Self-citationNaderi, S., & Blomhoff, H. K. (1999) · Blood · doi:10.1182/blood.v94.4.1348 · Cited by 49
Augmentation of antibody responses by retinoic acid and costimulatory molecules
Ross, A. C., Chen, Q., & Ma, Y. (2008) · Seminars in Immunology · doi:10.1016/j.smim.2008.08.004 · Cited by 48
Self-citationGangopadhyay, N. N., Moldoveanu, Z., & Stephensen, C. B. (1996) · Journal of Nutrition · doi:10.1093/jn/126.12.2960 · Cited by 46
Chang, S., Cha, H., Chang, J., Ko, H., Yang, H., MALISSEN, B., Iwata, M., & Kweon, M. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.11.006 · Cited by 45
Carotene and Vitamin A: The Anti-Infective Action of Carotene
Green, H. N., & Mellanby, E. (1930) · PubMed Central · Cited by 41
Menning, A., Loddenkemper, C., Westendorf, A. M., Szilagyi, B., Buer, J., Siewert, C., Hamann, A., & Huehn, J. (2010) · European Journal of Immunology · doi:10.1002/eji.200939938 · Cited by 38
Chen, Q., & Ross, A. C. (2007) · Cellular Immunology · doi:10.1016/j.cellimm.2007.11.001 · Cited by 38
Self-citationMa, Y., & Ross, A. C. (2009) · Clinical and Vaccine Immunology · doi:10.1128/cvi.00282-09 · Cited by 34
Self-citationTaking a Daily Vitamin to Prevent Type 1 Diabetes?
Wasserfall, C. H., & Atkinson, M. A. (2008) · Diabetes · doi:10.2337/db08-1479 · Cited by 18
The vitamin A and mortality paradigm: past, present, and future
Semba, R. D. (2001) · Näringsforskning · doi:10.3402/fnr.v45i0.1786 · Cited by 13
Nutrition and Disease: the Interaction of Clinical and Experimental Work
(1934) · Nature · doi:10.1038/134830b0 · Cited by 12
Sankaranarayanan, S., Ma, Y., Bryson, M. C., Li, N., & Ross, A. C. (2007) · Journal of Nutrition · doi:10.1093/jn/137.5.1229 · Cited by 11
Self-citationRetinol and retinyl esters in rabbit bone marrow and blood leukocytes
Skrede, B., Olafsdottir, A. E., Blomhoff, R., & Norum, K. R. (1993) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365519309092548 · Cited by 6
Progress in reducing global measles deaths: 1999-2004.
(2006) · PubMed · Cited by 6
Research works printed but not linked: 1
- Menning, 2010, Retinoic acid-induced gut tropism improves the protective capacity of Treg in acute but not in chronic gut inflammation, Eur J Immunol, 40, 2539, 10.1002/eji.200939938 · DOI
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Metadata
- Authors
- Ross, A. C.
- Affiliations
- Pennsylvania State University (US)
- Corresponding author
- Ross, A Catharine
- ORCID
- Ross, A Catharine
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2012-11
- Volume
- 96
- Issue
- 5
- Pages
- 1166S-1172S
- ISSN
- 0002-9165 (ISSN-L)
- PMC
- PMC3471201
- OpenAlex
- W2170235819
- Cited by
- 261
- References
- 75
- Citations by year
- 2026: 18 · 2025: 32 · 2024: 12 · 2023: 13 · 2022: 14 · 2021: 19 · 2020: 23 · 2019: 21 · 2018: 16 · 2017: 19 · 2016: 18 · 2015: 20 · 2014: 23 · 2013: 9 · 2012: 2
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (DK-41479)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK041479, R56DK041479, DK41479)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD066982, R01HD066982)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- vitamin A, retinoic acid, T cell immunity, regulatory T cells, T cell differentiation, T cell migration, mucosal immunity, T cell-dependent antibody response, vitamin A deficiency, inflammation, retinol, beta-carotene, T cell activation
- MeSH terms
- Animals, B-Lymphocytes, Cell Differentiation, Humans, Intestines, Tretinoin, Vitamin A, T-Lymphocyte Subsets, Immunity, Mucosal, T-Lymphocytes, Regulatory
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