Intestinal Lymphatic Endothelial Cells Produce R-Spondin3

Scientific Reports
Reiki OgasawaraTakanori Teshima

Abstract

The R-Spondin (R-Spo) family regulates WNT signaling and stimulates the proliferation and differentiation of intestinal stem cells (ISCs). R-Spo plays a critical role in maintaining intestinal homeostasis, but endogenous producers of R-Spo in the intestine remain to be investigated. We found that R-Spo3 was the major R-Spo family member produced in the intestine and it was predominantly produced by CD45-CD90+CD31+ lymphatic endothelial cells (LECs) in the lamina propria of the intestinal mucosa. Transcriptome analysis demonstrated that LECs highly expressed R-Spo receptor, Lgr5, suggesting an autocrine stimulatory loop in LECs. LECs were significantly reduced in number, and their R-Spo3 production was impaired in intestinal graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. The impaired production of R-Spo3 in the intestine may be a novel mechanism of delayed tissue repair and defective mucosal defense in intestinal GVHD. We demonstrate a novel role of intestinal LECs in producing R-Spondin3 to maintain intestinal homeostasis.

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Citations

Jul 3, 2020·Science Translational Medicine·Takahide AraTakanori Teshima
Sep 5, 2020·Nature Cell Biology·Neil McCarthyRamesh A Shivdasani
Dec 10, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Anne S Ten HoveWouter J de Jonge
Jun 9, 2021·Nature Communications·Vincenza CifarelliNada A Abumrad
Jun 8, 2021·Frontiers in Cell and Developmental Biology·Vangelis BonisHelmuth Gehart
Jul 3, 2021·International Journal of Molecular Sciences·Ljuba C PonomarevAn Zwijsen
Jan 2, 2021·Cell Regeneration·Guoli ZhuRongwen Xi
Aug 10, 2021·Blood·Ronjon Chakraverty, Takanori Teshima

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Datasets Mentioned

BETA
GE104979

Methods Mentioned

BETA
PCR
flow cytometry
ELISA
IECs
ubiquitination
dissection
FACS
Assay

Software Mentioned

ImageJ
Gene Spring GX
GraphPad
Prism

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