ArticleBMC gastroenterology2015
WNT5A transforms intestinal CD8αα⁺ IELs into an unconventional phenotype with pro-inflammatory features.
Article in BMC gastroenterology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed, 4 citations in OpenAlex.
- Targeting TARDBP to Restore Colonic Barrier Integrity in Ulcerative Colitis via NFATC1 mRNA Destabilization.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2026Article
- From bench to bedside: targeting lymphocyte activation gene 3 as a therapeutic strategy for autoimmune diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- Weak Cytotoxic T Cells Activation Predicts Low-Grade Dysplasia Persistence in Ulcerative Colitis.Clinical and translational gastroenterology · 2019Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIntestinal intraepithelial lymphocytes that reside within the epithelium of the intestine form one of the main branches of the immune system. A majority of IELs express CD8α homodimer together with other molecules associated with immune regulation. Growing evidence points to the WNT signaling pathway as a pivotal piece in the immune balance and focuses on its direct regulation in intestinal epithelium. Therefore we decided to investigate its role in IELs' immune status determination.
methodDSS colitis was induced in male C57BL mice. IELs were isolated from colon samples using mechanical dissociation followed by percoll gradient purification and Magnetic-activated cell sorting. Phenotype and cytokine production and condition with Wnts were analyzed by flow cytometry, real-time PCR or ELISA. Proliferation of lymphocytes were evaluated using CFSE dilution. Cell responses after WNT pathway interference were also evaluated.
resultsNon-canonical WNT pathway elements represented by FZD5, WNT5A and NFATc1 were remarkably elevated in colitis IELs. The non-canonical WNT5A skewed them into a pro-inflammatory category as measured by inhibitory cell surface marker LAG3, LY49E, NKG2A and activated marker CD69 and FASL. Gaining of a pro-inflammatory marker was correlated with increased IFN-γ production but not TNF whilst decreased TGF-β and IL-10. Both interrupting WNT5A/PKC pathway and adding canonical WNT stimulants could curtail its immune-activating effect.
conclusionCanonical and non-canonical WNT signals act in opposing manners concerning determining CD8αα(+) IELs immune status. Targeting non-canonical WNT pathway may be promising in tackling inflammatory bowel disease.
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