Researchers at the University of Toronto have discovered how a brief disruption to a molecular pathway in the guts of mice before they are born can compromise immunity in adulthood to a common and often deadly intestinal virus.
The researchers found that in utero inhibition of molecular signalling in the “lymphotoxin pathway,” long known as important in the development of the immune system, prevented a robust antibody response in adult mice to rotavirus. In humans, rotavirus causes an estimated 215,000 deaths annually, mostly in the developing world.
That early disruption limits the ability of the immune system to later trigger and generate production of Immunoglobulin A (IgA) antibodies, the researchers showed. It also interferes with the nature and function of cells in the gut that support the antibody response, called mesenteric lymph node stromal cells. The research was recently published in the journal Science Immunology.
“It was surprising that these non-immune stromal cells were so important to the immune response,” says Jennifer Gommerman, a professor of immunology in U of T’s Faculty of Medicine and principal investigator on the study.
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Photo: Post-doctoral researcher Conglei Li and Professor Jennifer Gommerman recently published their findings in the journal Science Immunology (photo by Jim Oldfield)