Research Article: Vitamin A and D in allergy: from experimental animal models and cellular studies to human disease

Date Published: February 20, 2018

Publisher: Springer Medizin

Author(s): Karin Hufnagl, Erika Jensen-Jarolim.


Vitamins A and D are able to modulate innate and adaptive immune responses and may therefore influence the development and the course of allergic diseases.

This article reviews the current evidence for the experimental effects of vitamins A and D in vivo in animal models and on immune cells in vitro, and discusses their translational implication. A systematic literature search over the last 10 years was performed using MEDLINE and PubMed databases.

Deficiencies of vitamin A or vitamin D in mouse models of allergic asthma seem to exacerbate allergic symptoms along with enhanced lung inflammation and Th2 cytokine production. In contrast, supplementation regimes especially with vitamin D were able to attenuate symptoms in therapeutic mouse models. The active metabolites retinoic acid (RA) and 1,25-dihydroxyvitamin D3 (VD3) induced tolerogenic dendritic cells (DCs) and up-regulated T‑regulatory cells in the allergic sensitization phase, which likely contributes to tolerance induction. Additionally, RA and VD3 maintained the stability of eosinophils and mast cells in the effector phase, thereby reducing allergic mediator release. Thus, both active vitamin metabolites RA and VD3 are able to influence allergic immune responses at several immunological sites.

Animal studies predict that vitamin A and D may also be attractive players in the control of allergy in humans. Whether these experimental observations can be translated to the human situation remains open, as results from clinical trials are controversial.

Partial Text

Vitamins and their metabolites regulate tissue growth, differentiation and embryonic development and have an important control function in the immune homeostasis by influencing both innate and adaptive immune responses. Vitamins A and D are distinct from other vitamins as their metabolites, retinoic acid (RA) and 1,25-dihydroxyvitamin D3 (VD3), are synthesized from precursors by different body tissues and they exert their effects on target cells by binding to nuclear hormone receptors.

The immunomodulatory potential of RA and VD3 was investigated since long [9] and recently their general influence on immune cells was reviewed in detail [1, 6]. Here we review reports on the innate and adaptive immune cells which are key players in allergic diseases.

In recent decades animal models have significantly contributed to the understanding of pathophysiologic mechanisms of allergic diseases such as asthma, anaphylaxis or food allergy [23]. Here we will concentrate on animal models of vitamin deficiency or supplementation that operate with and reflect on vitamin A or vitamin D contents that are taken up via the diet.

There are a number of studies that focus on the in vivo administration of the major vitamin metabolites RA and VD3 and the effects of such treatment on immune cells of the innate as well as adaptive immune system.

The findings from in vivo animal studies suggest that vitamin A and D seem to have a major impact on immune cells as well as on the development, and in the case of vitamin D even on the treatment of allergic Th2-dominated diseases. The question remains whether these findings can be translated to the human situation, especially concerning the dosage of vitamin supplementation in connection with adequate vitamin status [6, 32]. Nonetheless, in some of the studies conducted in mice the doses of vitamins were comparable to those applied in humans [26, 38].

The manifold impact of vitamin A and D on immune cell responses and profound evidence from animal studies provide hope that these molecules can help control allergy. More randomized controlled human studies are needed to underpin the potential of these vitamins and their metabolites in prevention or therapy of Th2-dominant allergic diseases including asthma. We propose that more emphasis should be put on the determination of the vitamin status of allergic patients and, especially for vitamin D, on prophylaxis in early life or during pregnancy.




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