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.
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 SCIDmice after infection than in wild-type mice. The number of EC cells and the amount of 5-HT was significantly increased after reconstitution of SCIDmice 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.
Authors: Vinton S Chadwick; Wangxue Chen; Dairu Shu; Barbara Paulus; Peter Bethwaite; Andy Tie; Ian Wilson Journal: Gastroenterology Date: 2002-06 Impact factor: 22.682
Authors: Michael Höpfner; Andreas P Sutter; Alexander Huether; Gudrun Ahnert-Hilger; Hans Scherübl Journal: BMC Cancer Date: 2004-05-21 Impact factor: 4.430
Authors: Marco Zucchelli; Michael Camilleri; Anna Nixon Andreasson; Francesca Bresso; Aldona Dlugosz; Jonas Halfvarson; Leif Törkvist; Peter T Schmidt; Pontus Karling; Bodil Ohlsson; Richard H Duerr; Magnus Simren; Greger Lindberg; Lars Agreus; Paula Carlson; Alan R Zinsmeister; Mauro D'Amato Journal: Gut Date: 2011-06-02 Impact factor: 23.059
Authors: Gordon W Moran; Fiona C Leslie; Scott E Levison; J Worthington; John T McLaughlin Journal: Therap Adv Gastroenterol Date: 2008-07 Impact factor: 4.409
Authors: M Yasuda; S Kato; N Yamanaka; M Iimori; K Matsumoto; D Utsumi; Y Kitahara; K Amagase; S Horie; K Takeuchi Journal: Br J Pharmacol Date: 2013-03 Impact factor: 8.739