Novel molecule may contribute to intestinal health

New data suggests that a novel molecule appears to be involved in the intestine’s response to infection. The study was a collaboration between researchers at Washington University School of Medicine in St. Louis and the Institut Curie in Paris. It appears in the March 13 issue of the journal Nature.

“This is the first identified function for this molecule,” says co-senior author Susan Gilfillan, Ph.D., research instructor in pathology and immunology at the School of Medicine. “Our findings suggest that this molecule may play a fundamental role in gut immunology.”

When a virus enters the body, proteins called antigens appear on the surface of cells and alert the immune system to infection. A molecule called MR1, which was discovered eight years ago, appears to be very similar to the main category of molecules that deliver antigens to the cell surface, called major histocompatibility complex class I (MHC Class I). However, its function is not yet understood.

To learn more about MR1, Gilfillan and colleagues developed a strain of mice lacking the molecule. The mice failed to develop a small population of immune cells known as mucosal-associated invariant t cells (MAIT cells). MAIT cells were just recently discovered by the study’s other co-senior author, Olivier Lantz, Ph.D., at the Institut Curie in Paris. The current study presents the first extensive characterization of these cells.

“These results help us begin to understand the function of MR1 and the role of MAIT cells in immunology,” Gilfillan says. “Both are found not only in mice but also in humans and other animals, such as cows, which implies that they probably are very important.”

The team also discovered that MAIT cells appear to be primarily located in the mucous membrane of the intestine, or gut. Moreover, mice lacking bacteria normally found in the gut do not have MAIT cells.

From these results, Gilfillan and colleagues conclude that MAIT cells rely on both MR1 and intestinal bacteria. In addition, the results imply that MR1 and MAIT cells play a critical role in the intestine’s response to infection. The team plans to continue investigating these interactions and also to explore whether MR1 and MAIT are involved in fighting infections in other organs lined with mucous-producing cells, including the lungs.

“It’s possible that MR1 and MAIT cells are involved in a variety of diseases of the gut, particularly those relating to microorganisms that reside in the intestine,” Gilfillan says. “We also expect this line of research will be of particular interest for general mucosal immunology, and may prove useful in studying other organ systems as well.”

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Treiner E, Duban L, Bahram S, Radosavljevic M, Wanner V, Tilloy F, Affaticati P, Gilfillan S, Lantz O. Selection of evolutionarily conserved mucosal-associated invariant T (MAIT) cells by MR1. Nature, March 13, 2003.

Funding from Association de la Recherche Contre la Cander, Fondation de la recherché Medicale, INSERM and Section Medicale de l’Institut Curie supported this research.