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.
- 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
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