Intestinal Lymphatic Endothelial Cells Produce R-Spondin3

Reiki Ogasawara, Daigo Hashimoto, Shunsuke Kimura, Eiko Hayase, Takahide Ara, Shuichiro Takahashi, Hiroyuki Ohigashi, Kosuke Yoshioka, Takahiro Tateno, Emi Yokoyama, Ko Ebata, Takeshi Kondo, Junichi Sugita, Masahiro Onozawa, Toshihiko Iwanaga, Takanori Teshima

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number10719
JournalScientific reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1
Externally publishedYes

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Endothelial Cells
Intestines
Graft vs Host Disease
Homeostasis
Hematopoietic Stem Cell Transplantation
Gene Expression Profiling
Intestinal Mucosa
Mucous Membrane
Stem Cells

ASJC Scopus subject areas

  • General

Cite this

Ogasawara, R., Hashimoto, D., Kimura, S., Hayase, E., Ara, T., Takahashi, S., ... Teshima, T. (2018). Intestinal Lymphatic Endothelial Cells Produce R-Spondin3. Scientific reports, 8(1), [10719]. https://doi.org/10.1038/s41598-018-29100-7

Intestinal Lymphatic Endothelial Cells Produce R-Spondin3. / Ogasawara, Reiki; Hashimoto, Daigo; Kimura, Shunsuke; Hayase, Eiko; Ara, Takahide; Takahashi, Shuichiro; Ohigashi, Hiroyuki; Yoshioka, Kosuke; Tateno, Takahiro; Yokoyama, Emi; Ebata, Ko; Kondo, Takeshi; Sugita, Junichi; Onozawa, Masahiro; Iwanaga, Toshihiko; Teshima, Takanori.

In: Scientific reports, Vol. 8, No. 1, 10719, 01.12.2018.

Research output: Contribution to journalArticle

Ogasawara, R, Hashimoto, D, Kimura, S, Hayase, E, Ara, T, Takahashi, S, Ohigashi, H, Yoshioka, K, Tateno, T, Yokoyama, E, Ebata, K, Kondo, T, Sugita, J, Onozawa, M, Iwanaga, T & Teshima, T 2018, 'Intestinal Lymphatic Endothelial Cells Produce R-Spondin3', Scientific reports, vol. 8, no. 1, 10719. https://doi.org/10.1038/s41598-018-29100-7
Ogasawara R, Hashimoto D, Kimura S, Hayase E, Ara T, Takahashi S et al. Intestinal Lymphatic Endothelial Cells Produce R-Spondin3. Scientific reports. 2018 Dec 1;8(1). 10719. https://doi.org/10.1038/s41598-018-29100-7
Ogasawara, Reiki ; Hashimoto, Daigo ; Kimura, Shunsuke ; Hayase, Eiko ; Ara, Takahide ; Takahashi, Shuichiro ; Ohigashi, Hiroyuki ; Yoshioka, Kosuke ; Tateno, Takahiro ; Yokoyama, Emi ; Ebata, Ko ; Kondo, Takeshi ; Sugita, Junichi ; Onozawa, Masahiro ; Iwanaga, Toshihiko ; Teshima, Takanori. / Intestinal Lymphatic Endothelial Cells Produce R-Spondin3. In: Scientific reports. 2018 ; Vol. 8, No. 1.
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