title: Colony stimulating factor-1 dependence of paneth cell development in the mouse small intestine.
abstract: OBJECTIVE
  Paneth cells (PCs) secrete defensins and antimicrobial enzymes that contribute to innate immunity against pathogen infections within the mucosa of the small intestine. We examined the role of colony stimulating factor-1 (CSF-1) in PC development.
  
  
  METHODS
  CSF-1-deficient and CSF-1 receptor (CSF-1R)-deficient mice and administration of neutralizing anti-CSF-1R antibody were used to study the requirement of CSF-1 for the development of epithelial cells of the small intestine. CSF-1 transgenic reporter mice and mice that express only the membrane-spanning, cell-surface CSF-1 isoform were used to investigate regulation by systemic versus local CSF-1.
  
  
  RESULTS
  Mice deficient in CSF-1 or CSF-1R had greatly reduced numbers of mature PCs. PCs express the CSF-1R, and administration of anti-CSF-1R antibody to neonatal mice significantly reduced the number of PCs. Analysis of transgenic CSF-1 reporter mice showed that CSF-1-expressing cells are in close proximity to PCs. CSF-1/CSF-1R-deficient mice also had reduced numbers of the proliferating epithelial cell progenitors and lamina propria macrophages. Expression of the membrane-spanning, cell-surface CSF-1 isoform in CSF-1-deficient mice completely rescued the deficiencies of PCs, proliferating progenitors, and lamina propria macrophages.
  
  
  CONCLUSIONS
  These results indicate local regulation by CSF-1 of PC development, either directly, in a juxtacrine/paracrine manner, or indirectly, by lamina propria macrophages. Therefore, CSF-1R hyperstimulation could be involved in hyperproliferative disorders of the small intestine, such as Crohn's disease and ulcerative colitis.
authors.affiliation: Peter MacCallum Cancer Centre, East Melbourne, Australia.
authors.forename: Duy
authors.initials: D
authors.lastname: Huynh
authors.forename: Xu-Ming
authors.initials: XM
authors.lastname: Dai
authors.forename: Sayan
authors.initials: S
authors.lastname: Nandi
authors.forename: Sally
authors.initials: S
authors.lastname: Lightowler
authors.forename: Melanie
authors.initials: M
authors.lastname: Trivett
authors.forename: Chee-Kai
authors.initials: CK
authors.lastname: Chan
authors.forename: Ivan
authors.initials: I
authors.lastname: Bertoncello
authors.forename: Robert G
authors.initials: RG
authors.lastname: Ramsay
authors.forename: E Richard
authors.initials: ER
authors.lastname: Stanley
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism* / Q000473:pathology; D016173:Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019879:Paneth Cells / Q000378:metabolism* / Q000473:pathology; D019899:Paracrine Communication; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism
chemical_list: C530105:Ccnd1 protein, mouse; C493597:Lgr5 protein, mouse; D043562:Receptors, G-Protein-Coupled; D019938:Cyclin D1; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor