Review Article

Vitamin effects on the immune system: vitamins A and D take centre stage

  • Nature Reviews Immunology volume 8, pages 685698 (2008)
  • doi:10.1038/nri2378
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Abstract

Vitamins are essential constituents of our diet that have long been known to influence the immune system. Vitamins A and D have received particular attention in recent years as these vitamins have been shown to have an unexpected and crucial effect on the immune response. We present and discuss our current understanding of the essential roles of vitamins in modulating a broad range of immune processes, such as lymphocyte activation and proliferation, T-helper-cell differentiation, tissue-specific lymphocyte homing, the production of specific antibody isotypes and regulation of the immune response. Finally, we discuss the clinical potential of vitamin A and D metabolites for modulating tissue-specific immune responses and for preventing and/or treating inflammation and autoimmunity.

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Acknowledgements

We thank S. Davis for editorial assistance and E. Villablanca for critical reading of this manuscript. J.R.M. is grateful to I. Ramos for constant support. J.R.M. is supported by grants from the Crohn's & Colitis Foundation of America, the Cancer Research Institute, the Howard M. Goodman Fellowship and the Center for the Study of IBD (DK 43351). M.I. is supported by the Grants-in-Aid from Japan Society for the Promotion of Science and the Ministry of Education, Culture, Sports, Science and Technology, the Naito Foundation and the Uehara Memorial Foundation. U.H.v.A. is supported by National Institutes of Health grants AI061663, AI069259, AI072252, HL56949 and AR42689.

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Affiliations

  1. Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.

    • J. Rodrigo Mora
  2. Laboratory of Biodefense Research, Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, Kagawa, 769-2193, Japan.

    • Makoto Iwata
  3. Immune Disease Institute & Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.

    • Ulrich H. von Andrian

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  2. Search for Makoto Iwata in:

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Corresponding authors

Correspondence to J. Rodrigo Mora or Ulrich H. von Andrian.

Supplementary information

PDF files

  1. 1.

    Supplementary information S1 (table)

    Overview of vitamins and the immune system.

Glossary

Stellate cells

(Also known as Ito cells). Types of pericytes found in the hepatic perisinusoidal space that are the main reservoirs of retinol in the liver.

Intestinal epithelial cells

(IECs). A tight monolayer of cells covering the luminal surface of the intestine. They are specialized in the absorption of nutrients and also serve as a mechanical and immunological barrier with the external environment (the intestinal lumen).

Peyer's patches

Groups of lymphoid nodules present in the small intestine (usually the ileum). They are found massed together on the intestinal wall, opposite the line of attachment of the mesentery. Peyer's patches consist of a dome area, B-cell follicles and interfollicular T-cell areas.

Mesenteric lymph nodes

(MLNs). Lymph nodes located at the base of the mesentery. They collect lymph (including cells and antigens) draining from the intestinal mucosa.

TH17 cells

(T helper 17 cells). A subset of CD4+ T helper cells that produce interleukin-17 (IL-17) and are thought to be important in inflammatory and autoimmune diseases. Their generation involves TGFβ, IL-6, IL-23 or IL-21, IL-1β and the transcription factor RORγt.

TReg cells

(Regulatory T cells). Specialized types of CD4+ T cells that can suppress the effector responses of other immune cells. These cells provide a crucial mechanism for the maintenance of peripheral self-tolerance and are characterized by the expression of the transcription factor forkhead box P3.

Systemic lupus erythematosus

(SLE). An autoimmune disease in which autoantibodies specific for DNA, RNA or proteins associated with nucleic acids form immune complexes. These complexes damage small blood vessels, especially in the kidneys. Patients with SLE generally have abnormal B- and T-cell function as well as rashes, arthritis, kidney disease and central-nervous-system involvement.

Antibody-secreting cells

(ASCs). Cells specialized in secreting immunoglobulins. Although they originate from activated B cells, ASCs lose the expression of surface immunoglobulins and other B-cell markers and upregulate plasma cell markers, such as CD138 in mice or CD27 in humans.

TR1 cells

(T regulatory type 1 cells) A population of regulatory T cells that arises in the periphery after an encounter with antigen in the presence of interleukin-10 (IL-10) and that regulates immune responses through the secretion of IL-10 and transforming growth factor-β. They suppress T-cell responses, downregulate the expression of co-stimulatory molecules and pro-inflammatory cytokines by antigen-presenting cells and favour the production of IgD, IgA and IgG by B cells.

Gut-associated lymphoid tissue

(GALT). Lymphoid structure associated with the intestinal mucosa, including cryptopatches, isolated lymphoid follicles, Peyer's patches and caecal and colonic patches.

Small intestinal lamina propria

Connective tissue between the intestinal epithelium and the intestinal muscularis mucosae layer, which contains various myeloid and lymphoid cells, including macrophages, dendritic cells, T cells and B cells.

Colonic patches

Structures resembling Peyer's patches that are scattered throughout the colon. They have been implicated in the generation of colonic immune responses.

Experimental allergic encephalomyelitis

(EAE). An experimental model of the human disease multiple sclerosis. Autoimmune disease is induced in experimental animals by immunization with myelin or peptides derived from myelin. The animals develop a paralytic disease with inflammation and demyelination in the brain and spinal cord.

Type 1 diabetes

A chronic autoimmune disease that is characterized by the T-cell-mediated destruction of β cells (which secrete insulin) in the pancreas. Patients with type 1 diabetes develop hyperglycaemia and can develop diabetes-associated complications in multiple organ systems, owing to a lack of insulin. Diabetes in non-obese diabetic mice is a model of type I diabetes.

Atherosclerosis

A chronic disorder of the arterial wall characterized by endothelial damage that gradually induces deposits of cholesterol, cellular debris, calcium and other substances. These deposits eventually lead to plaque formation and arterial stiffness.

Ischaemia-reperfusion injury

(IRI). Cellular damage caused by the return of blood supply to a tissue after a period of inadequate blood supply. The absence of oxygen and nutrients causes cellular damage, such that restoration of the blood flow results in inflammation.

Rheumatoid arthritis

An immunological disorder that is characterized by symmetrical polyarthritis, often progressing to crippling deformation after years of synovitis. It is associated with systemic immune activation, with the presence of acute-phase reactants in the peripheral blood and with rheumatoid factor (immunoglobulins specific for IgG), which form immune complexes that are deposited in many tissues.

Inflammatory bowel disease

(IBD). A chronic condition of the intestine that is characterized by severe inflammation and mucosal destruction. The most common forms in humans are ulcerative colitis and Crohn's disease, which are believed to be T helper 2 (TH2)- and TH1-type diseases, respectively. However, interleukin-23 and TH17 cells have also recently been shown to be involved in the pathology of IBD.

Graft-versus-host disease

(GVHD). An immune response mounted against the recipient of an allograft by immunocompetent donor T cells that are derived from the graft. Typically, it is seen in the context of allogeneic bone-marrow transplantation.