Article1 min read·Published Apr 2024Older

WNT2B Deficiency Causes Enhanced Susceptibility to Colitis Due to Increased Inflammatory Cytokine Production

Part of Inflammatory & Immune-Mediated GI Disease 9 items

pubmed.ncbi.nlm.nih.gov

Michael Helmrath

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. 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. 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. 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.

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Article · Apr 2024 · 1 min read

In brief

WNT2B deficiency increases susceptibility to colitis through dysregulated inflammatory cytokine production rather than epithelial defects. Mouse models and human organoids demonstrate elevated CXCR4 and IL6 expression, with enhanced neutrophil infiltration driving severe inflammatory injury in the colon.

Written by the GCMD Library team from the article.

Michael Helmrath

Statements in this article

Humans with WNT2B deficiency have severe intestinal disease, including significant inflammatory injury.
EstablishedBackground & Aims
Mice with WNT2B deficiency had normal baseline intestinal histology in both small intestine and colon.
ResearchResults
WNT2B-deficient mice showed enhanced susceptibility to dextran sodium sulfate (DSS) colitis due to an increased early injury response.
ResearchResults
Intestinal stem cell markers were decreased in WNT2B-deficient mice, but epithelial proliferation was similar to control subjects.
ResearchResults
WNT2B knockout mice showed an enhanced inflammatory signature after DSS treatment.
ResearchResults
WNT2B knockout colon tissue had increased levels of CXCR4 and IL6.
ResearchResults
Human WNT2B-deficient intestinal organoids had increased levels of CXCR4 and IL6.
ResearchResults
Biopsy tissue from humans with WNT2B deficiency showed increased neutrophils.
ResearchResults
WNT2B is important for regulation of inflammation in the intestine.
EstablishedConclusions
Absence of WNT2B leads to increased expression of inflammatory cytokines and increased susceptibility to gastrointestinal inflammation, particularly in the colon.
ResearchConclusions