CD4+ T cell-mediated immunological control of enterochromaffin cell hyperplasia and 5-hydroxytryptamine production in enteric infection. Issue 7 (15th February 2007)

• Record Type: Journal Article
• 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
• Is Part Of: Gut. Volume 56:Issue 7(2007)
• Page Start: 949
• Page End: 957
• Publication Date: 2007-02-15
• Subjects: ANOVA, analysis of variance -- CGA, chromogranin A -- EC, enterochromaffin -- GI, gastrointestinal -- 5-HT, 5-hydroxytryptamine -- IBS, irritable bowel syndrome -- IL, interleukin -- IL4R, interleukin 4 receptor -- IL-13Rα1, interleukin 13 receptor α1-chain -- LCM, laser capture microdissection -- PBS, phophate-buffered saline -- PI, post-infectious -- RT, room temperature -- RT-PCR, reverse transcription PCR -- SCID, severe combined immunodeficient -- Th2, T helper 2; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gut.2006.103226
• Languages: English
• ISSNs: 0017-5749

Abstract

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 α1-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.