Colony Stimulating Factor-1 Dependence of Paneth Cell Development in the Mouse Small Intestine

Duy Huynh, Xu Ming Dai, Sayan Nandi, Sally Lightowler, Melanie Trivett, Chee Kai Chan, Ivan Bertoncello, Robert G. Ramsay, E. Richard Stanley

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Background & Aims: 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.

Original languageEnglish
JournalGastroenterology
Volume137
Issue number1
DOIs
Publication statusPublished - Jul 2009
Externally publishedYes

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Paneth Cells
Macrophage Colony-Stimulating Factor
Small Intestine
Macrophage Colony-Stimulating Factor Receptors
Mucous Membrane
Macrophages
Protein Isoforms
Epithelial Cells
Cell Membrane
Defensins
Antibodies
Ulcerative Colitis
Innate Immunity
Crohn Disease

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Colony Stimulating Factor-1 Dependence of Paneth Cell Development in the Mouse Small Intestine. / Huynh, Duy; Dai, Xu Ming; Nandi, Sayan; Lightowler, Sally; Trivett, Melanie; Chan, Chee Kai; Bertoncello, Ivan; Ramsay, Robert G.; Stanley, E. Richard.

In: Gastroenterology, Vol. 137, No. 1, 07.2009.

Research output: Contribution to journalArticle

Huynh, D, Dai, XM, Nandi, S, Lightowler, S, Trivett, M, Chan, CK, Bertoncello, I, Ramsay, RG & Stanley, ER 2009, 'Colony Stimulating Factor-1 Dependence of Paneth Cell Development in the Mouse Small Intestine', Gastroenterology, vol. 137, no. 1. https://doi.org/10.1053/j.gastro.2009.03.004
Huynh, Duy ; Dai, Xu Ming ; Nandi, Sayan ; Lightowler, Sally ; Trivett, Melanie ; Chan, Chee Kai ; Bertoncello, Ivan ; Ramsay, Robert G. ; Stanley, E. Richard. / Colony Stimulating Factor-1 Dependence of Paneth Cell Development in the Mouse Small Intestine. In: Gastroenterology. 2009 ; Vol. 137, No. 1.
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AU - Trivett, Melanie

AU - Chan, Chee Kai

AU - Bertoncello, Ivan

AU - Ramsay, Robert G.

AU - Stanley, E. Richard

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AB - Background & Aims: 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.

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