This electron microscope image depicts a single MMC9 cell. Within the large nucleus in the middle, chromosomes appear as blackish strings. The dense round shape in the top right corner is a granule that may be filled with protein mediators.
Study finds cell type that amplifies severe food allergy reactions
Researchers have discovered a new cell type that appears to drive life-threatening food allergies and may help explain why some people get severe allergic reactions and others do not.
Reporting their study data Sept. 22 in the journal Immunity, scientists at Cincinnati Children’s say their findings in mice should also provide insights into new therapeutic strategies and diagnostics for food allergies and anaphylactic shock triggered by the immune antibody IgE (immunoglobulin E).
The authors report that IL-9-producing mucosal mast cells (MMC9 cells) produce large amounts of the inflammatory immune protein interlukin 9 (IL-9), which amplifies anaphylactic shock in response to ingested food. Prior to this study, the primary cellular source of IL-9 was unknown.
“Our study suggests that although you need to have some level of IgE to trigger a food allergy response, you also have to produce MMC9 cells to get a severe response and anaphylaxis,” says Yui-Hsi Wang, PhD, lead investigator and a researcher in the Division of Allergy and Immunology at Cincinnati Children’s. “Without these cells you will not get severe food allergies.”
More clues in the food allergy mystery
Set off by certain foods like peanuts, shell fish and a host of others, IgE-associated food sensitivity prompts the immune systems of some children to surge out of control. Unless there is immediate medical intervention, this can trigger a molecular chain reaction in the intestines and other organs – leading to diarrhea, hypothermia, respiratory distress and shock.
About 40 percent of children have some IgE-associated food sensitivity, but only 8 percent of the 40 percent develop the severe food reactions that can lead to anaphylactic shock, according to Wang.
“Unfortunately the best medical intervention for these allergies remains avoiding the foods that cause them,” he said. “We don’t know why some patients develop such a strong response and why some don’t. This is where we as basic scientists are coming in to see if we can use mouse models to learn this, because mice are very much like humans.”
Wang and his colleagues suspect that some people are wired genetically to have higher or lower susceptibility to severe IgE-related allergic reactions. Still, it also remains unknown exactly how genetics contributes to these molecular chain reactions.
Intestinal MMC9 cells lead to severe reactions
In this study, based on several distinct strains of genetically bred mice, the scientists observed that after allergic sensitization, some mouse strains generated large populations of MMC9 cells while other strains did not. Mice that did not produce MMC9 cells exhibited only minor allergic responses. Mice that produced intestinal MMC9 cells all had severe allergic reactions, regardless of whether they had low or high levels of IgE.
The production of MMC9 cells required the presence of type-2 CD4+ T helper immune cells and the proteins interlukin-4 and STAT6. By producing significant amounts of IL-9, the MMC9 cells caused mastocytosis and the production of mast cells, which may migrate out of the intestines to other organs as they secrete histamines and other molecules that cause anaphylaxis.
Researchers also analyzed human biopsy samples and found molecular signatures that indicate that the identification of MMC9 cells in mice is relevant to the development of human food allergies. Now the team is working to find the human equivalent (orthologue) of the MMC9 cells they found in their mouse models.
Eventually, this research could lead to new blood tests that would show which patients are at higher risk for severe food allergies, and possibly to improved treatments for food allergy.
Also working with Wang on the study were co-first authors Chun-Yu Chen, PhD and Jee-Boong Lee, PhD from the Division of Allergy and Immunology at Cincinnati Children’s.