Study Uncovers How Vitamin A Infiltrates Immune Cells in the Gut

Researchers at UT Southwestern Medical Center, specializing in immunology and genetics, have unveiled the mechanism by which vitamin A gains access to immune cells within the intestinal tract. These revelations hold promise for advancing the treatment of digestive disorders and potentially enhancing the effectiveness of certain vaccines.

“Now that we know more about this important aspect of immune function, we may eventually be able to manipulate how vitamin A is delivered to the immune system for disease treatment or prevention,” said Howard Hughes Medical Institute Investigator Lora Hooper, Ph.D., Chair of Immunology at UT Southwestern.

Dr. Hooper, Professor of Immunology, Microbiology, and in the Center for the Genetics of Host Defense at UT Southwestern, explains that vitamin A, a fat-soluble nutrient, is a special type of nutrient that our body needs. It is a very important element for every tissue in the body. Our body changes it into retinol and retinoic acid before it is used.

Vitamin A is really important for all parts of our body. It is vital for the adaptive immune system, an element of the broader immune system that responds to particular pathogens based on immunological memory, the kind created by exposure to disease or vaccinations.

Dr. Hooper and other scientists knew that some special cells in our intestines could change retinol into retinoic acid. But they didn’t know how these cells got retinol in the first place. It was a mystery. Dr. Hooper’s lab studies how the tiny living things in our intestines, called bacteria, affect our bodies and those of other animals.

Ye-Ji Bang, a scientist in the Hooper Lab, and her colleagues explored a group of proteins called serum amyloid A, which some organs produce when the body is fighting infections. They used special techniques to figure out which proteins on the surface of cells these proteins stuck to, and they found one called LDL receptor-related protein 1 (LRP1).

Over 30 years ago, Dr. Joachim Herz, who works at UT Southwestern and directs the Center for Translational Neurodegeneration Research, made an important discovery. He is also a professor of Molecular Genetics, Neurology, and Neuroscience. Dr. Herz’s research group studies how genes related to the LDL receptor family work in the brain and blood vessels. It’s all about understanding the minutiae of how these receptors send signals and transport molecules within the body.

This kind of research is really significant. In fact, a similar discovery related to the LDL receptor, also made at UT Southwestern, led to Dr. Michael Brown and Dr. Joseph Goldstein winning the Nobel Prize in Physiology or Medicine in 1985.

Doctors Bang, Hooper, Herz, and their team found that LRP1 was located on specific cells in the intestines, known as intestinal myeloid cells. It seemed like LRP1 played a role in bringing retinol into these cells. To understand this better, the researchers used special genetic techniques to remove the gene responsible for LRP1 in mice. This prevented their myeloid cells from taking in the vitamin A derivative.

Dr. Hooper explained that when they did this, the adaptive immune system in the mice’s intestines basically vanished. This included crucial elements of the immune system like T and B cells, and a crucial molecule, immunoglobulin A, which are all vital for adaptive immunity. To test this further, the researchers exposed these mice to a Salmonella infection. The mice that did not have LRP1 were quickly overcome by the infection.

The study, reported in the journal Science, indicates that LRP1 serves as the transport system for retinol to get inside myeloid cells. According to Dr. Hooper, if scientists can figure out a method to block this process, it might help reduce the immune response in diseases that cause inflammation in the intestines, like inflammatory bowel disease and Crohn’s disease. On the other hand, if they can find a way to increase LRP1’s activity, it could potentially make oral vaccines work better by boosting the immune response.

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