The intestinal immune system must constantly maintain the difficult balance between fighting infections and simultaneously tolerating harmless or useful germs, and our food components.
Vitamin A deficiency is not only associated with immune dysfunctions in the GIT, but also with systemic disorders of the immune system.
In addition to its well-described role for adaptive immunity, there is a recent and expanding pool of insights about the importance of vitamin A in its role as a modulator for cells of the innate immune system, such as dendritic and lymphatic cells.
Especially the active metabolite, atRA (all-trans-retinoic acid), which is produced from vitamin A by intestinal cells is able to
AtRA, therefore, plays an essential role in maintaining immune tolerance (to food and microbial antigens) and tissue homeostasis.
A study published recently on the murine model shows that atRA influences the immune responses in the intestine by controlling the expression of a protein called HIC1.
HIC1 stands for "Hypermethylated in cancer 1" because it was first discovered in cancer cells. However, it also occurs in normal cells, such as those of the innate immune system, where it is involved in the regulation of gene expression. Active vitamin A affects HIC1 activity, and mice in which the HIC1 gene was selectively deleted, were more susceptible to intestinal bacterial infections. Thus, the atRA-dependent transcription factor HIC1 seems to be essential for maintaining healthy immune defense in the "barrier zone" of the intestinal mucosa.
The authors of the study conclude that there is a molecular link between vitamin A and the immune response of innate lymphatic cells. They hope that further research on this topic will open up new strategies to protect against infections or other GIT disorders such as food allergies and irritable bowel syndrome.
1. Czarnewski P et al. Retinoic Acid and Its Role in Modulating Intestinal Innate Immunity. Nutrients. 2017;9(1):68. doi:10.3390/nu9010068.
2. Burrows K et al. HIC1 left retinoic acid signaling to group 3 innate lymphoid cell-dependent regulation of intestinal immunity and homeostasis. PLOS Pathogens. 2018; 14 (2): e1006869 DOI: 10.1371/journal.ppat.1006869
3. PLOS. "Scientists find the molecular link between Vitamin A derivative and mouse intestinal health: HIC1 protein could serve as the potential target to protect against intestinal disease." ScienceDaily, February 22, 2018.