Molecular link uncovered between Vitamin A and intestinal health
New research from Monash University has found a signalling molecule that helps maintain intestinal health in mice. Published in PLoS Pathogens, these findings could provide new ways to fight disease.
Monash Biomedicine Discovery Institute’s Professor Colby Zaph and an international research team have shown the active form of vitamin A regulates immune system responses in the mouse intestine.
It does so by controlling activity of a protein in innate lymphoid cells, called ‘Hypermethylated in cancer 1’ (HIC1).
With further research, these findings could open up new strategies to protect against infection and intestinal imbalance, which can lead to conditions such as food allergy and irritable bowel syndrome.
Professor Zaph explained the significance of this revelation.
“Vitamin A has long been known to play a central role in the balance between intestinal immune health and disease, but the precise molecular mechanisms of how it affected immune cells was unknown,” Professor Zaph said.
“Identifying HIC1 provides a potential target to modulate intestinal inflammation.”
How it works
The intestinal immune system must strike a balance between fighting infection and maintaining tolerance to harmless or beneficial microbes and food particles.
Previous research has shown that the active form of Vitamin A – produced from dietary vitamin A by some intestinal cells and called all-trans-retinoic acid (atRA) – helps maintain this balance in mice by regulating the activity of innate lymphoid cells. However, the molecular details of this process have been unclear.
The new study focused on the protein HIC1, which was first identified in cancer cells, but also helps regulate gene expression in normal cells. The research team had previously shown that atRA influences HIC1 activity and that HIC1 helps maintain intestinal health in mice. Now, they have investigated the molecular details of HIC1’s role.
The researchers deleted the HIC1 gene in certain innate lymphoid cells in the mouse intestine and found that this increased the susceptibility of the mice to infection with the bacterium Citrobacter rodentium, which is similar to pathogenic E. coli species that infect humans. Further investigation revealed that the increased susceptibility was due to a reduction in production by the innate lymphoid cells of IL-22, a protein that plays a key role in the intestinal immune response.
Read the full paper in PLoS Pathogens titled HIC1 links retinoic acid signalling to group 3 innate lymphoid cell-dependent regulation of intestinal immunity and homeostasis.
This story has been adapted from a PLoS Pathogens press release.
About the Monash Biomedicine Discovery Institute
Committed to making the discoveries that will relieve the future burden of disease, the newly established Monash Biomedicine Discovery Institute at Monash University brings together more than 120 internationally-renowned research teams. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.