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. 2007 Jul;56(7):949-57.
doi: 10.1136/gut.2006.103226. Epub 2007 Feb 15.

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

Huaqing Wang  1 , Justin Steeds, Yasuaki Motomura, Yikang Deng, Monica Verma-Gandhu, Rami T El-Sharkawy, John T McLaughlin, Richard K Grencis, Waliul I Khan
Affiliations

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

Huaqing Wang et al. Gut. 2007 Jul.

Abstract

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(+) 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(+) 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 alpha1-chain on EC cells.

Conclusion: These results show an important immunoendocrine axis in the gut, where secretory products from CD4(+) 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.

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Conflict of interest statement

Competing interests: None.

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