Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Dual epithelial and immune cell function of Dvl1 regulates gut microbiota composition and intestinal homeostasis
Haim Belinson, … , Richard M. Locksley, Ophir D. Klein
Haim Belinson, … , Richard M. Locksley, Ophir D. Klein
Published July 7, 2016
Citation Information: JCI Insight. 2016;1(10):e85395. https://doi.org/10.1172/jci.insight.85395.
View: Text | PDF
Research Article Gastroenterology

Dual epithelial and immune cell function of Dvl1 regulates gut microbiota composition and intestinal homeostasis

  • Text
  • PDF
Abstract

Homeostasis of the gastrointestinal (GI) tract is controlled by complex interactions between epithelial and immune cells and the resident microbiota. Here, we studied the role of Wnt signaling in GI homeostasis using Disheveled 1 knockout (Dvl1–/–) mice, which display an increase in whole gut transit time. This phenotype is associated with a reduction and mislocalization of Paneth cells and an increase in CD8+ T cells in the lamina propria. Bone marrow chimera experiments demonstrated that GI dysfunction requires abnormalities in both epithelial and immune cells. Dvl1–/– mice exhibit a significantly distinct GI microbiota, and manipulation of the gut microbiota in mutant mice rescued the GI transit abnormality without correcting the Paneth and CD8+ T cell abnormalities. Moreover, manipulation of the gut microbiota in wild-type mice induced a GI transit abnormality akin to that seen in Dvl1–/– mice. Together, these data indicate that microbiota manipulation can overcome host dysfunction to correct GI transit abnormalities. Our findings illustrate a mechanism by which the epithelium and immune system coregulate gut microbiota composition to promote normal GI function.

Authors

Haim Belinson, Adam K. Savage, Douglas Fadrosh, Yien-Ming Kuo, Din Lin, Ricardo Valladares, Ysbrand Nusse, Anthony Wynshaw-Boris, Susan V. Lynch, Richard M. Locksley, Ophir D. Klein

×

Figure 4

Abnormal Paneth cell number and positioning in Dvl1–/– mice.

Options: View larger image (or click on image) Download as PowerPoint
Abnormal Paneth cell number and positioning in Dvl1–/– mice.
The gastroi...
The gastrointestinal (GI) tract of wild-type (WT) and Disheveled 1 knockout (Dvl1–/–) mice were processed for histology, RT-PCR, and in situ hybridization. (A) Sections from the ileum of 12-week-old mice were stained with DAPI (nuclei) and immunostained for E-cadherin and lysozyme, and representative images are shown. (B) Sections from the ileum of 12-week-old mice were stained with DAPI and immunostained for MMP7, and representative images are shown. Scale bar: 100 μm. (C) Quantification of the number of DAPI+lysozyme+ cells per crypt are presented as box plot (Bonferroni *P < 0.004 for comparing the results of the Dvl1–/– with those of the WT mice). (D) Sections from the GI tract of 8-week-old mice were processed for in situ hybridization and probed for Defa5 and representative images are shown. Scale bar: 200 μm. (E) Sections from the in vitro gut organoids were stained with DAPI and immunostained for lysozyme and EphB2, and representative images are shown. Scale bar: 100 μm. (F) Quantification of the numbers of DAPI+lysozyme+EphB2+ cells per crypt are presented as box plot (Bonferroni *P < 0.003 for comparing the results of the Dvl1–/– with those of the WT mice). (G) RNA from ileum and proximal colon (PC) of 12-week-old WT and Dvl1–/– mice was extracted and RT-PCR was performed. The levels of Atoh1/Math1, Lyz1, Defa5, Defa1, EphB2, and EphB3 were normalized to Gapdh and are presented as box plot (n = 5, Bonferroni *P < 0.05, **P < 0.005 for comparing the results of the Dvl1–/– with those of the WT mice).

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts