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WNT2B Deficiency Causes Enhanced Susceptibility to Colitis Due to Increased Inflammatory Cytokine Production.
- Source :
-
Cellular and molecular gastroenterology and hepatology [Cell Mol Gastroenterol Hepatol] 2024; Vol. 18 (2), pp. 101349. Date of Electronic Publication: 2024 Apr 30. - Publication Year :
- 2024
-
Abstract
- Background & Aims: Humans with WNT2B deficiency have severe intestinal disease, including significant inflammatory injury, highlighting a critical role for WNT2B. We sought to understand how WNT2B contributes to intestinal homeostasis.<br />Methods: We investigated the intestinal health of Wnt2b knock out (KO) mice. We assessed the baseline histology and health of the small intestine and colon, and the impact of inflammatory challenge using dextran sodium sulfate (DSS). We also evaluated human intestinal tissue.<br />Results: Mice with WNT2B deficiency had normal baseline histology but enhanced susceptibility to DSS colitis because of an increased early injury response. Although intestinal stem cells markers were decreased, epithelial proliferation was similar to control subjects. Wnt2b KO mice showed an enhanced inflammatory signature after DSS treatment. Wnt2b KO colon and human WNT2B-deficient organoids had increased levels of CXCR4 and IL6, and biopsy tissue from humans showed increased neutrophils.<br />Conclusions: WNT2B is important for regulation of inflammation in the intestine. Absence of WNT2B leads to increased expression of inflammatory cytokines and increased susceptibility to gastrointestinal inflammation, particularly in the colon.<br /> (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Humans
Mice
Colon pathology
Colon metabolism
Disease Models, Animal
Disease Susceptibility
Glycoproteins
Intestinal Mucosa pathology
Intestinal Mucosa metabolism
Intestinal Mucosa immunology
Mice, Knockout
Organoids metabolism
Organoids pathology
Receptors, CXCR4 metabolism
Receptors, CXCR4 genetics
Colitis pathology
Colitis chemically induced
Colitis metabolism
Cytokines metabolism
Dextran Sulfate toxicity
Wnt Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2352-345X
- Volume :
- 18
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cellular and molecular gastroenterology and hepatology
- Publication Type :
- Academic Journal
- Accession number :
- 38697357
- Full Text :
- https://doi.org/10.1016/j.jcmgh.2024.04.006