Home Immunity UTSW scientists reveal how vitamin A enters immune cells in the gut: newsroom

UTSW scientists reveal how vitamin A enters immune cells in the gut: newsroom



A microscopic image of cells expressing LRP1 (green) in the intestine (cell nuclei are in blue).

DALLAS – September 16, 2021 – Immunologists and geneticists at UT Southwestern Medical Center have discovered how vitamin A enters immune cells in the gut – findings that may offer insight for treating digestive diseases and possibly help improve the effectiveness of certain vaccines.

A microscope image

Dietary vitamin A becomes retinol, which is internalized in cells by LRP1 and promotes adaptive immunity in the gut. Credit: courtesy of the Hooper Lab using BioRender.com

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

Vitamin A – a fat-soluble nutrient that the body converts into a molecule called retinol and then into retinoic acid before it can be used – is important for every tissue in the body, said Dr. Hooper, professor of immunology, microbiology and cancer. Center for Host Defense Genetics at UT Southwestern. This is particularly crucial for the adaptive immune system, a subset of the larger immune system that responds to specific pathogens based on immunological memory, the type formed by exposure to disease or vaccines.

Although researchers knew that certain intestinal immune cells called myeloid cells can convert retinol to retinoic acid, how they acquire retinol to perform this task was a mystery, said Dr Hooper, whose lab studies how bacteria in the gut. residents influence the biology of humans and other mammals. hosts.

Lead author Ye-Ji Bang, Ph.D., postdoctoral fellow at Hooper Lab, and colleagues focused on serum amyloid A proteins, a family of retinol-binding proteins that certain organs produce during infections. They used biochemical techniques to determine which cell surface proteins they attached to and identified LDL receptor-bound protein 1 (LRP1).

Lora Hooper, Ph.D.

Dr Hooper speaks at a launch ceremony for the Graduate School of Biomedical Sciences at UTSW, which trains more than 1,000 learners per year, including more than 500 postdoctoral fellows.

LRP1 was discovered over 30 years ago by another UT Southwestern researcher, Joachim Herz, director of the Center for Translational Neurodegeneration Research and professor of molecular genetics, neurology and neuroscience. The Herz lab focuses on the molecular mechanisms by which members of the LDL receptor gene family function as signaling and endocytosis receptors in the brain and vessel wall. The discovery of the LDL receptor, made at UT Southwestern, enabled Michael Brown, MD, and Joseph Goldstein, MD, to win the Nobel Prize in Physiology or Medicine in 1985.

Drs. Bang, Hooper, Herz and their colleagues showed that LRP1 was present on intestinal myeloid cells, where it appeared to carry retinol inside. When the researchers used genetic techniques to suppress the gene for this receptor in mice, preventing their myeloid cells from absorbing the vitamin A derivative, the adaptive immune system in their gut all but disappeared, Dr. Hooper said. T and B cells and the immunoglobulin A molecule, essential components of adaptive immunity, were significantly reduced. The researchers then compared the response to Salmonella infection between mice with LRP1 and those without. Those who lacked the receptor were quickly conquered by the infection.

Lora Hooper, Ph.D.

Lora Hooper, Ph.D., Chair in Immunology, is one of 13 Distinguished HHMI Researchers at UT Southwestern. The Hooper Lab is studying how resident gut bacteria influence the biology of humans and other mammalian hosts.

The conclusions, published in Sciencesuggest that LRP1 is the vehicle by which retinol enters myeloid cells. If researchers can develop a way to inhibit this process, Dr Hooper said, it could dampen the immune response in inflammatory diseases that affect the intestines, such as inflammatory bowel disease and Crohn’s disease. Alternatively, finding a way to improve LRP1 activity could boost immune activity, making oral vaccines more effective.

Other UTSW researchers who contributed to this study include Zehan Hu, Yun Li, Sureka Gattu, Kelly A. Ruhn, and Prithvi Raj.

This work was supported by grants from the National Institutes of Health (R01 DK070855), the Welch Foundation (I-1874), the Walter M. and Helen D. Bader Center for Research on Arthritis and Autoimmune Diseases, and the Howard Hughes Medical Institute. .

Dr Brown, Professor of Molecular Genetics and Internal Medicine, is the WA (Monty) Moncrief Professor in Cholesterol and Arteriosclerosis Research and the Paul J. Thomas Chair in Medicine.

Dr. Goldstein, Professor of Molecular Genetics and Professor of Internal Medicine, is Professor of the Julie and Louis A. Beecherl, Jr. Distinguished Chair in Biomedical Research, and the Paul J. Thomas Chair in Medicine.

Dr Herz, member of Brain Institute Peter O’Donnell Jr., holds the Presbyterian Village North Foundation Honorary Chair in Therapeutic Research in Alzheimer’s Disease and the Thomas O. and Cinda Hicks Family Honorary Chair in Alzheimer’s Disease Research.

Dr. Hooper holds the Jonathan W. Uhr, MD Emeritus Chair in Immunology and is the Nancy Cain and Jeffrey A. Marcus Fellow in Medical Research, in honor of Dr. Bill S. Vowell. She is also a member of Harold C. Simmons Comprehensive Cancer Center.

About UT Southwestern Medical Center

UT Southwestern, one of the nation’s leading academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has been awarded six Nobel Prizes and includes 25 members of the National Academy of Sciences, 16 members of the National Academy of Medicine and 13 researchers of the Howard Hughes Medical Institute. The full-time faculty of over 2,800 is responsible for groundbreaking medical advancements and is committed to rapidly translating science-driven research into new clinical treatments. Doctors at UT Southwestern provide care in approximately 80 specialties to more than 117,000 inpatients, more than 360,000 emergency room cases and supervise nearly 3 million outpatient visits per year.