The scientists from Purdue University have revealed that retinoic acid - a metabolite that comes from digested vitamin A - is necessary for two of the three types of innate immune cells that reside in the intestine to find their proper place.
"It is known that vitamin A deficiencies lead to increased susceptibility to disease and low concentrations of immune cells in the mucosal barrier that lines the intestines," said Professor Chang Kim, who led the research.
"We wanted to find the specific role the vitamin plays in the immune system and how it influences the cells and biological processes,” said Kim. “The more we understand the details of how the immune system works, the better we will be able to design treatments for infection, and autoimmune and inflammatory diseases."
Within the immune system there are two categories of cells that work together to rid the body of infection: fast acting innate immune cells and adaptive immune cells that arrive later, but are specific to the pathogen and more effective at killing or counteracting it.
While it is known that innate cells, including lymphoid cells, are concentrated in the intestines, it has been unknown how these cells find their way there, Kim said.
Indeed, innate lymphoid cells first gather in the lymph nodes before traveling to their final destination, he said – adding that this is where retinoic acid acts upon two of the three subsets destined for the intestines.
Writing in the journal Immunity, Kim and his colleagues found that retinoic acid activates specific receptors in the cells that act as homing devices for the intestines.
As the innate immune cells then travel through the circulatory system, the receptors grab onto and bind to molecules in the intestines and keep the cells in place, he said.
"It is important that these cells be concentrated in mucosal barrier tissues, as opposed to scattered throughout the body, because these tissues are the point of entry for many infections from bacteria, viruses and parasites," said Kim.
"Now that we have established the system of migration for these cells, we can play with it a little and see what changes the behaviour and function of the cells,” he said.
Vitamin A is the key?
While the new work finds that vitamin A is essential for directing innate immune cells to the mucosal barriers in the intestine, earlier work from Kim and colleagues showed that vitamin A also regulates the migration of adaptive T-cells.
"It is interesting that both innate and adaptive immune cells share a vitamin A-regulated pathway for migration," he said. "However, there are distinct differences and programs that regulate the migration of the different types of cells and even subsets within them."
However, vitamin A is not the only vitamin known to regulate the migration of immune cells, noted the team.
Indeed, vitamin D has been shown to work in a similar way to guide immune cells to the skin, added Kim.
"We all know that what we eat significantly affects our overall health and immunity," he said.
"While there are other important regulators of immune system function, the role vitamins play is significant. How this works on a molecular level is a growing field of study."
Kim next plans to study in greater detail the molecular pathways involved in the migration of innate lymphoid cells to the intestine and other organs.
Published online ahead of print, doi: 10.1016/j.immuni.2015.06.009
"Retinoic Acid Differentially Regulates the Migration of Innate Lymphoid Cell Subsets to the Gut"
Authors: Myung H. Kim, et al