Basic—Alimentary TractColony Stimulating Factor-1 Dependence of Paneth Cell Development in the Mouse Small Intestine
Section snippets
Mice
Csf1op/+24 and Csf1r−/+29 mice, backcrossed on the FVB/NJ background for at least 10 generations,30 were used to generate homozygous mutant and WT (+/+) control mice. Csf1op/op;TgCS5/+ mice, exclusively expressing the cell-surface isoform of CSF-1 from the TgN(CSCSF1)5Ers (TgCS5) transgene30 and TgN(Csf1-Z)9Ers homozygote (TgZ9/TgZ9) mice expressing β-gal,32 which in both cases have transgene expression driven by the same Csf1 promoter and first intron regulatory region, were also on the FVB/NJ
Disrupted Morphology in the SIs of Csf1op/op and Csf1r−/− Mice
Two-week-old Csf1op/op and Csf1r−/Csf1r− (Csf1r−/−) mutant FVB/NJ pups were smaller than their WT littermates, as described previously,30, 40 and their SIs were shorter (Supplementary Figure 1). Tissue sections stained with the neutral mucin stain, PAS (Figure 1A), or the acid mucin stain, AB (Supplementary Figure 2), showed an aberrant goblet cell staining in the SI villi of mutant mice compared with WT littermates. The mucin-stained vacuoles in mutant villi were approximately double the
Discussion
PCs play a critical role in the innate immune response to bacteria.16, 17, 18 CSF-1 regulation of macrophages,25 trophoblastic cells,47 and Langerhans cells31 is important for innate immunity in many tissues.48 We have shown that both PCs and macrophages in the SI express high levels of the CSF-1R and that, as for macrophages,25 the development of PCs largely depends on the CSF-1R. Furthermore, CSF-1–synthesizing cells are found in close proximity to PCs, and normal regulation of PC development
Acknowledgments
The authors thank Drs Paul Jubinsky and Y.G. Yeung for critically reviewing the manuscript, Dr Xiao-Hua Zong and Ranu Basu for technical assistance, and Dr Jenny Karlsson Sjöberg (Karolinska Institutet, Sweden) for the Cryptdin 2 and CRS4C antibodies.
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Conflicts of interest The authors disclose no conflicts.
Funding This work was supported by the National Health and Medical Research Council of Australia, the Cancer Council of Victoria (R.G.R.), National Institutes of Health grant CA32551 (E.R.S.), the Albert Einstein College of Medicine Cancer Center grant 5P30-CA13330, an American Society of Hematology Fellow Scholar Award (X.-M.D.), and a Leukaemia and Lymphoma Society Special Fellow Award (X.-M.D.).