CD4 super(+) T cell-mediated immunological control of enterochromaffin cell hyperplasia and 5-hydroxytryptamine production in enteric infection

• Published in: Gut Vol. 56; no. 7; pp. 949 - 957
• Main Authors: Wang, Huaqing, Steeds, Justin, Motomura, Yasuaki, Deng, Yikang, Verma-Gandhu, Monica, El-Sharkawy, Rami T, McLaughlin, John T, Grencis, Richard K, Khan, Waliul I
• Format: Journal Article
• Language: English
• Published: 01.07.2007
• Subjects: Nematoda
• ISSN: 0017-5749; 1468-3288

BACKGROUND: Enterochromaffin (EC) cells are dispersed throughout the gastrointestinal (GI) mucosa and are the main source of 5-hydroxytryptamine (5-HT) in the gut. 5-HT has been implicated in the pathophysiology of several GI disorders, but the mechanisms regulating 5-HT production in the gut are unknown. Aim: To investigate the role of CD4 super(+) T cells in the production of 5-HT using a model of enteric parasitic infection. METHODS: and results: Severe combined immunodeficient (SCID) mice and their wild-type controls were infected with the nematode Trichuris muris and killed on various days after infection to study colonic EC cells and 5-HT production. The number of EC cells and the amount of 5-HT produced were significantly higher in infected wild-type mice than in non-infected mice. The number of EC cells and the amount of 5-HT after infection were significantly lower in SCID mice after infection than in wild-type mice. The number of EC cells and the amount of 5-HT was significantly increased after reconstitution of SCID mice with CD4 super(+) T cells from infected mice and this was accompanied by an upregulation of colonic CD3 T cells and T helper 2 (Th2) cytokines. Laser capture microdissection-based molecular and immunofluorescence techniques revealed the presence of interleukin 13 receptor alpha 1-chain on EC cells. CONCLUSION: These results show an important immunoendocrine axis in the gut, where secretory products from CD4 super(+) T cells interact with EC cells to enhance the production of 5-HT in the gut via Th2-based mechanisms. These results show new insights into the mechanisms of gut function, which may ultimately lead to improved therapeutic strategies in functional and inflammatory disorders of the GI tract.