P008 Differences in macrophage infiltration and Wnt ligands expression between stricturing and penetrating behaviour in Crohn’s disease
Bibliographic record
Abstract
Fibrosis and fistula development constitute the main complications associated to Crohn′s disease. The Wnt signalling pathway induces fibroblast activation and EMT which are involved in these complications. We aim to analyse here the pattern of Wnt ligands expression in surgical resections from stenotic and fistulising CD patients and to determine the potential role of these ligands in favouring fistula development over fibrosis. CD patients (n = 43) were categorised according to Montreal classification. mRNA was isolated from resections of patients presenting a stricturing (B2) or a penetrating (B3) behaviour or from unaffected mucosa of patients with colorectal cancer. The expression of macrophage markers (CD206, CD86 and CD16), all Wnt ligands and Frizzled receptors, and DKK1, Lgr5, and cmyc was analysed by RT-PCR or flow cytometry. ECM deposition was analysed by staining. Correlations between data were analysed using Pearson’s correlation coefficient (*p < 0.05). The mRNA expression of EMT genes were analysed in isolated crypts treated with Wnt2b peptide for 7 h. A higher percentage of CD16 (B2: 36.12 ± 5.8%; B3:69.7 ± 24.4%) or CD86 (B2: 30.58 ± 10.9%; B3:88.8 ± 18.4%) positive macrophages and a higher mRNA expression of pro-inflammatory cytokines (IL-1, IL-6, Table 1) was detected in intestinal tissue from B3 compared with B2 CD patients. A higher mRNA expression of Vimentin and lower expression of E-cadherin was detected in CD patients compared with controls (Table 1) while no differences in the expression of these markers were detected between the fistulising and stenotic behaviour which exhibited a similar ECM deposition. CD patients presented a generalised overexpression of WNT (Wnt2, Wnt3, and Wnt6) ligands with the exception of Wnt2b which was up-regulated in the fistulising group and down-regulated in the stenotic group (p < 0.01, B3 vs. B2, Table 1) compared with control. The expression of DKK1, cmyc and Lgr5 were higher in B3 behaviour. The expression of Wnt2b significantly correlated with CD16 (r = 0.8155, p = 0.0007*), vimentin (r = 0.6315, p = 0.0087*), and STAT3 (r = 0.4919, p < 0.0001*), only in intestinal tissue from the B3 group. Wnt2 exogenous administration produce an increased mRNA expression in EMT-related genes (Vimentin and Snail1/2). Relative (Gene/b-actin) mRNA expression (fold induction vs. control group) of genes with detectable levels. Data are expressed as mean ± SEM with n ≥ 7 in all groups and analysed by ANOVA + Kewman–Keuls test. (*p < 0.05 vs. B2.). A different pattern of macrophage infiltration and Wnt ligands expression is detected in CD patients presenting a B2 or a B3 behaviour. Wnt2b, probably released from CD16 positive macrophages, may play a role in fistula development over fibrosis in CD patients.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.009 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".