Mechanisms of intestinal pathology from food allergies
Roles of different lymphoid tissues in regulating enteropathy
Graduate School of Agricultural and Life Sciences / Faculty of Agriculture
University of Tokyo researchers have shown that Interleukin-4 (IL-4) is required for the onset of food allergic enteropathy (intestinal inflammation). The research group of Project Researcher Haruyo Adachi (nee Nakajima) of the Graduate School of Agricultural and Life Sciences Research Center for Food Safety and Associate Professor Satoshi Hachimura and Professor Hiroshi Kiyono of the Institute of Medical Science used transgenic mice often employed as a model for food allergies to show that IL-4, a cytokine produced by a type of white blood cell (CD4+ T-cell) that reacts only to the presence of ovalbumin, is essential for the onset of enteropathy. Ovalbumin is a protein component found in egg white, and the CD4+ T-cells in this mouse model have receptors that bind only to this protein.
Continued administration of ovalbumin to mice suffering from food allergy after the emergence of inflammation results in these T-cells becoming tolerant and the mouse overcoming the enteropathy. In order to identify the immune system mechanisms involved in the onset and suppression of enteropathy, the research group created transgenic mice deficient in various lymphoid tissues. They showed that 1) in the intestinal immune tissues, mesenteric lymph nodes are critically required for the onset of enteritis, but Peyer’s patches, lymph node-like organs in the intestinal tract, react quickly to the ingested ovalbumin and function cooperatively with mesenteric lymph nodes; 2) the systemic immune tissue, spleen, promptly acquired tolerance to ingested ovalbumin and are not involved in the development of enteropathy; 3) in the mesenteric lymph nodes, the persistent inflammatory responses continue after the establishment of strong systemic tolerance to ingested ovalbumin. The minor and persistent inflammatory responses found in the mesenteric lymph nodes, after tolerance induction in this model may be involved in the reemergence of enteropathy.
The immune system induces the conflicting responses of inflammation and tolerance to ingested food. When this complex immune system balance breaks down, food allergies are caused in patients, but the detailed mechanism remains unknown. The present study has elucidated which tissues are involved and how they are interrelated, and is a major contribution to the development of safe and effective treatments based on solid scientific evidence.
Press release (Japanese)
Haruyo Nakajima-Adachi, Akira Kikuchi, Yoko Fujimura, Kyoko Shibahara, Tsuyoshi Makino, Masako Toda, Shuichi Kaminogawa, Ryuichiro Sato, Hiroshi Kiyono, Satoshi Hachimura, et.al.,
“Peyer’s patches and mesenteric lymph nodes cooperatively promote enteropathy in a mouse model of food allergy”,
PLoS One Online Edition: 2014/10/7 (Japan time), doi: 10.1371/journal.pone.0107492.