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CD4+ T cell-mediated immunological control of enterochromaffin cell hyperplasia and 5-hydroxytryptamine production in enteric infection
  1. Huaqing Wang1,
  2. Justin Steeds1,
  3. Yasuaki Motomura1,
  4. Yikang Deng1,
  5. Monica Verma-Gandhu1,
  6. Rami T El-Sharkawy1,
  7. John T McLaughlin2,
  8. Richard K Grencis3,
  9. Waliul I Khan1
  1. 1Intestinal Diseases Research Program, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
  2. 2Department of Gastrointestinal Sciences, University of Manchester, Manchester, UK
  3. 3Department of Immunology, University of Manchester, Manchester, UK
  1. Correspondence to:
    Dr W I Khan
    Department of Medicine, Room 3N5D, Health Science Centre, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5; khanwal{at}mcmaster.ca

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.

  • 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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Footnotes

  • Published Online First 15 February 2007

  • Competing interests: None.

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