title: CD4+ T cell-mediated immunological control of enterochromaffin cell hyperplasia and 5-hydroxytryptamine production in enteric infection.
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.
  
  
  OBJECTIVE
  To investigate the role of CD4(+) T cells in the production of 5-HT using a model of enteric parasitic infection.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Intestinal Diseases Research Program, Department of Medicine, Room 3N5D, Health Science Centre, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: Huaqing
authors.initials: H
authors.lastname: Wang
authors.forename: Justin
authors.initials: J
authors.lastname: Steeds
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Motomura
authors.forename: Yikang
authors.initials: Y
authors.lastname: Deng
authors.forename: Monica
authors.initials: M
authors.lastname: Verma-Gandhu
authors.forename: Rami T
authors.initials: RT
authors.lastname: El-Sharkawy
authors.forename: John T
authors.initials: JT
authors.lastname: McLaughlin
authors.forename: Richard K
authors.initials: RK
authors.lastname: Grencis
authors.forename: Waliul I
authors.initials: WI
authors.lastname: Khan
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003106:Colon / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004759:Enterochromaffin Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D006965:Hyperplasia / Q000276:immunology; D018793:Interleukin-13 / Q000096:biosynthesis; D053661:Interleukin-13 Receptor alpha1 Subunit / Q000378:metabolism; D015847:Interleukin-4 / Q000096:biosynthesis; D007411:Intestinal Diseases, Parasitic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D012701:Serotonin / Q000096:biosynthesis*; D018418:Th2 Cells / Q000276:immunology; D014257:Trichuriasis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000276:immunology
chemical_list: C508183:Il13ra1 protein, mouse; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4; D012701:Serotonin