October 31, 2014

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Fig. 1 In order to define the critical tissue(s) for induction of food allergic enteropathy in mice fed ovalbumin, the research group generated a variety of tissue-removed mice. The tissues removed from each group of mice were mesenteric lymph nodes (MLNs), Peyer’s patch (PPs), MLNs and PPs (pLNs), and the spleen (SP), respectively. Intestinal immune tissues, but not systemic tissue, play critical roles in establishment of the enteropathy.
© 2014 Haruyo Adachi

University of Tokyo researchers have shown that Interleukin-4 (IL-4) is required for the onset of enteritis (intestinal inflammation). The research group of Project Researcher Haruyo Adachi (née 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 genetically modified 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 enteritis. Ovalbumin is a protein 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 enteritis. In order to identify the immune system mechanisms involved in the onset and suppression of enteritis, the research group created genetically-modified mice deficient in various gut-associated lymphoid tissues. They showed that 1) mesenteric lymph nodes are 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 system and spleen are not involved in the onset of colitis between the administration of ovalbumin and the emergence of tolerance; 3) in the case that inflammation continues after the establishment of tolerance, the mesenteric lymph nodes may be involved in the reemergence of colitis.

The immune system induces the conflicting responses of inflammation and tolerance to ingested food. This complex immune system balance breaks down in the emergence of food allergies, 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.

Paper Information

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
Online Edition: PLoS One, October, 7, 2014 doi: 10.1371/journal.pone.0107492. eCollection 2014.
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