title: The goblet cell is the cellular source of the anti-microbial angiogenin 4 in the large intestine post Trichuris muris infection.
abstract: BACKGROUND
  Mouse angiogenin 4 (Ang4) has previously been described as a Paneth cell-derived antimicrobial peptide important in epithelial host defence in the small intestine. However, a source for Ang4 in the large intestine, which is devoid of Paneth cells, has not been defined.
  
  
  RESULTS
  Analysis was performed on Ang4 expression in colonic tissue by qPCR and immunohistochemistry following infection with the large intestine dwelling helminth parasite Trichuris muris. This demonstrated an increase in expression of the peptide following infection of resistant BALB/c mice. Further, histological analysis of colonic tissue revealed the cellular source of this Ang4 to be goblet cells. To elucidate the mechanism of Ang4 expression immunohistochemistry and qPCR for Ang4 was performed on colonic tissue from T. muris infected mouse mutants. Experiments comparing C3H/HeN and C3H/HeJ mice, which have a natural inactivating mutation of TLR4, revealed that Ang4 expression is TLR4 independent. Subsequent experiments with IL-13 and IL-4 receptor alpha deficient mice demonstrated that goblet cell expression of Ang4 is controlled either directly or indirectly by IL-13.
  
  
  CONCLUSIONS
  The cellular source of mouse Ang4 in the colon following T. muris infection is the goblet cell and expression is under the control of IL-13.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom. ruth.forman@manchester.ac.uk
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Forman
authors.forename: Matthew L
authors.initials: ML
authors.lastname: deSchoolmeester
authors.forename: Rebecca J M
authors.initials: RJ
authors.lastname: Hurst
authors.forename: Steven H
authors.initials: SH
authors.lastname: Wright
authors.forename: Alan D
authors.initials: AD
authors.lastname: Pemberton
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Else
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism*; D005786:Gene Expression Regulation; D020397:Goblet Cells / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007420:Intestine, Large / Q000469:parasitology* / Q000473:pathology*; D007421:Intestine, Small / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D051379:Mice; D019879:Paneth Cells / Q000378:metabolism / Q000473:pathology; D051192:Receptors, Pattern Recognition / Q000378:metabolism; D012259:Ribonuclease, Pancreatic / Q000235:genetics / Q000378:metabolism*; D014257:Trichuriasis / Q000378:metabolism / Q000469:parasitology / Q000473:pathology*; D014258:Trichuris / Q000502:physiology*
chemical_list: D000890:Anti-Infective Agents; D018793:Interleukin-13; D051192:Receptors, Pattern Recognition; D015847:Interleukin-4; C519253:Ang4 protein, mouse; D012259:Ribonuclease, Pancreatic