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

Overview

Journal Gastroenterology

Specialty Gastroenterology

Date 2009 Mar 24

PMID 19303020

Citations 36

Authors

Duy Huynh

Xu-Ming Dai

Sayan Nandi

Sally Lightowler

Melanie Trivett

Chee-Kai Chan

Ivan Bertoncello

Robert G Ramsay

E Richard Stanley

Affiliations

Soon will be listed here.

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.

Citing Articles

Microglial Depletion, a New Tool in Neuroinflammatory Disorders: Comparison of Pharmacological Inhibitors of the CSF-1R.

Guenoun D, Blaise N, Sellam A, Roupret-Serzec J, Jacquens A, Steenwinckel J Glia. 2024; 73(4):686-700.

PMID: 39719687 PMC: 11845850. DOI: 10.1002/glia.24664.

The microbiota control the neonatal WNT-ernet.

McPherson A, Meisel M Immunity. 2022; 55(12):2219-2222.

PMID: 36516814 PMC: 10165554. DOI: 10.1016/j.immuni.2022.11.005.

ST2 and CSF-1 as potential druggable targets of inflammatory bowel diseases: Results from two-sample Mendelian randomization study.

Mi J, Wu X, Bai X, Yang Y, Yang H Clin Transl Sci. 2022; 16(2):236-245.

PMID: 36333983 PMC: 9926074. DOI: 10.1111/cts.13442.

mediates enhancement of intestinal tumorigenesis caused by inactivation of .

Liu F, Bouznad N, Kaller M, Shi X, Konig J, Jaeckel S Int J Biol Sci. 2022; 18(14):5415-5437.

PMID: 36147476 PMC: 9461672. DOI: 10.7150/ijbs.75503.

IκBζ controls IL-17-triggered gene expression program in intestinal epithelial cells that restricts colonization of SFB and prevents Th17-associated pathologies.

Yamazaki S, Inohara N, Ohmuraya M, Tsuneoka Y, Yagita H, Katagiri T Mucosal Immunol. 2022; 15(6):1321-1337.

PMID: 35999460 PMC: 9705257. DOI: 10.1038/s41385-022-00554-3.

References

Huttner K, Selsted M, Ouellette A . Structure and diversity of the murine cryptdin gene family. Genomics. 1994; 19(3):448-53. DOI: 10.1006/geno.1994.1093. View

McLean I, Nakane P . Periodate-lysine-paraformaldehyde fixative. A new fixation for immunoelectron microscopy. J Histochem Cytochem. 1974; 22(12):1077-83. DOI: 10.1177/22.12.1077. View

Nandi S, Akhter M, Seifert M, Dai X, Stanley E . Developmental and functional significance of the CSF-1 proteoglycan chondroitin sulfate chain. Blood. 2005; 107(2):786-95. PMC: 1895624. DOI: 10.1182/blood-2005-05-1822. View

Cheng H, Leblond C . Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. I. Columnar cell. Am J Anat. 1974; 141(4):461-79. DOI: 10.1002/aja.1001410403. View

Wehkamp J, Stange E . Paneth cells and the innate immune response. Curr Opin Gastroenterol. 2006; 22(6):644-50. DOI: 10.1097/01.mog.0000245541.95408.86. View

Kiyohara H, Egami H, Shibata Y, Murata K, Ohshima S, Ogawa M . Light microscopic immunohistochemical analysis of the distribution of group II phospholipase A2 in human digestive organs. J Histochem Cytochem. 1992; 40(11):1659-64. DOI: 10.1177/40.11.1431054. View

Marsh M, Trier J . Morphology and cell proliferation of subepithelial fibroblasts in adult mouse jejunum. II. Radioautographic studies. Gastroenterology. 1974; 67(4):636-45. View

Hennighausen L, Wall R, Tillmann U, Li M, Furth P . Conditional gene expression in secretory tissues and skin of transgenic mice using the MMTV-LTR and the tetracycline responsive system. J Cell Biochem. 1995; 59(4):463-72. DOI: 10.1002/jcb.240590407. View

Ii M, Yamamoto H, Adachi Y, Maruyama Y, Shinomura Y . Role of matrix metalloproteinase-7 (matrilysin) in human cancer invasion, apoptosis, growth, and angiogenesis. Exp Biol Med (Maywood). 2005; 231(1):20-7. DOI: 10.1177/153537020623100103. View

10.

Guleria I, Pollard J . The trophoblast is a component of the innate immune system during pregnancy. Nat Med. 2000; 6(5):589-93. DOI: 10.1038/75074. View

11.

Murayama T, Yokode M, Kataoka H, Imabayashi T, Yoshida H, Sano H . Intraperitoneal administration of anti-c-fms monoclonal antibody prevents initial events of atherogenesis but does not reduce the size of advanced lesions in apolipoprotein E-deficient mice. Circulation. 1999; 99(13):1740-6. DOI: 10.1161/01.cir.99.13.1740. View

12.

Adegboyega P, Mifflin R, DiMari J, Saada J, Powell D . Immunohistochemical study of myofibroblasts in normal colonic mucosa, hyperplastic polyps, and adenomatous colorectal polyps. Arch Pathol Lab Med. 2002; 126(7):829-36. DOI: 10.5858/2002-126-0829-ISOMIN. View

13.

Elmes M . The Paneth cell population of the small intestine of the rat-effects of fasting and zinc deficiency on total count and on dithizone-reactive count. J Pathol. 1976; 118(3):183-91. DOI: 10.1002/path.1711180308. View

14.

Andreu P, Peignon G, Slomianny C, Taketo M, Colnot S, Robine S . A genetic study of the role of the Wnt/beta-catenin signalling in Paneth cell differentiation. Dev Biol. 2008; 324(2):288-96. DOI: 10.1016/j.ydbio.2008.09.027. View

15.

Cheng H . Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. IV. Paneth cells. Am J Anat. 1974; 141(4):521-35. DOI: 10.1002/aja.1001410406. View

16.

Garabedian E, Roberts L, McNevin M, Gordon J . Examining the role of Paneth cells in the small intestine by lineage ablation in transgenic mice. J Biol Chem. 1997; 272(38):23729-40. DOI: 10.1074/jbc.272.38.23729. View

17.

Wehkamp J, Harder J, Weichenthal M, Schwab M, Schaffeler E, Schlee M . NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal alpha-defensin expression. Gut. 2004; 53(11):1658-64. PMC: 1774270. DOI: 10.1136/gut.2003.032805. View

18.

Wehkamp J, Schmid M, Stange E . Defensins and other antimicrobial peptides in inflammatory bowel disease. Curr Opin Gastroenterol. 2007; 23(4):370-8. DOI: 10.1097/MOG.0b013e328136c580. View

19.

Sorokin S, Hoyt Jr R . PAS-lead hematoxylin as a stain for small-granule endocrine cell populations in the lungs, other pharyngeal derivatives and the gut. Anat Rec. 1978; 192(2):245-59. DOI: 10.1002/ar.1091920205. View

20.

Sweet M, Hume D . CSF-1 as a regulator of macrophage activation and immune responses. Arch Immunol Ther Exp (Warsz). 2003; 51(3):169-77. View