LA JOLLA INSTITUTE FOR ALLERGY & IMMUNOLOGY FINDING CITED AS KEY 2007 RESEARCH ADVANCE BY Nature Medicine
Prestigious Scientific Journal Names LIAI Discovery Among Year's Most Notable Advances
SAN DIEGO - January 24, 2008 - A finding by La Jolla Institute for Allergy & Immunology (LIAI) researchers that could one day lead to new avenues for treating inflammatory bowel diseases, rheumatoid arthritis and other autoimmune diseases has been cited by Nature Medicine as one of the key biomedical research advances of 2007. Nature Medicine is one of the world's most prestigious scientific journals for biomedical research and is respected internationally for the quality of its scientific papers.
The Institute's finding, based on laboratory studies in mice, demonstrated the role of a Vitamin A derivative, retinoic acid, in fighting inflammation, and it was originally published in the journal Science in June 2007. Hilde Cheroutre, Ph.D., led the research team, entirely from LIAI, in which Daniel Mucida, Ph.D., and Yunji Park, Ph.D., were key contributors. The finding is an important first step that, if eventually found to be safe and applicable in humans, points to the potential of new therapies using retinoic acid, already used to treat some types of leukemia, to treat various inflammatory and autoimmune diseases.
Nature Medicine's 2007 Year in Review section, which appeared in its December issue, discussed the LIAI finding in an article on Notable Advances highlighting key biomedical research findings in 10 areas during 2007. "Nature Medicine's recognition of the LIAI finding as a key advance further validates the importance of this exciting work," said Mitchell Kronenberg, Ph.D., LIAI president and scientific director. "Dr. Cheroutre and her team are continuing to delve further into this discovery which has opened a new frontier in inflammation research."
The article provided links to the scientific papers and publications where the findings were first reported. In some research areas, more than one scientific paper was cited, since various research groups around the world may have contributed to the advance. Dr. Cheroutre's lab was the first to publish that retinoic acid can cause increases in the number of anti-inflammatory cells in mice, which was reaffirmed by scientific papers published by several other research groups later in the year. Dr. Cheroutre's paper went one step further, however, by showing that retinoic acid can also reduce the number of inflammatory cells (TH-17 cells) - demonstrating that it plays a role in modulating the switch between reducing or increasing inflammatory cells.
Nature Medicine's editors said the research by Dr. Cheroutre's team and the other scientific groups was important because it revealed that the vitamin A metabolite retinoic acid affects immune regulation. "A hot area of research is the balancing act between so-called Th17 cells that promote autoimmunity and the anti-inflammatory regulatory T cells that dampen immune responses," the editors said in a written comment. "Dr. Cheroutre and her colleagues provided insight into how retinoic acid swings this balance towards the protective regulatory T cells that can prevent autoimmunity."
In addition to the LIAI finding, others highlighted in the article included research advances aimed at generating stem cells without destroying embryos; a discovery by Japanese researchers of a possible cellular trigger for lung cancer tumors, and possible new therapeutic targets for heart disease.
In the LIAI study, researchers showed that by manipulating the amount of retinoic acid in mice, they could decrease the number of pro-inflammatory T cells (TH-17 cells), a type of white blood cell responsible for several autoimmune and inflammatory diseases. Retinoic acid is a substance derived when Vitamin A is broken down in the body. The researchers were able to reduce inflammation in the mice by giving them more retinoic acid than they would have through normal body processes. Conversely, the number of inflammatory cells grew when the researchers blocked retinoic acid in the mice.
"We found that you can control inflammation in a living animal with retinoic acid or you can treat cells with retinoic acid in a test tube and transfer them to the organism to suppress inflammation in vivo," said Dr. Cheroutre. The mice in the study were successfully treated for inflammatory bowel disease, but researchers believe the retinoic acid manipulation will also affect other autoimmune and inflammatory bowel diseases. Dr. Cheroutre and her team are currently analyzing its impacts on type 1 diabetes in mice, and preliminary data indicate that retinoic acid has similar effects on human white blood cells when analyzed in test tubes.
About LIAI
Founded in 1988, the La Jolla Institute for Allergy and Immunology
is a non-profit medical research center dedicated to increasing
knowledge and improving human health through studies of the immune
system. Researchers at the institute carry out studies designed to
understand and develop cures for cancer, allergy and asthma, infectious
diseases, and autoimmune diseases such as diabetes, inflammatory bowel
disease and arthritis. The institute's research staff includes
approximately 100 Ph.Ds.
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