A96 MACROPHAGES DERIVED FROM BLOOD MONOCYTES OF PATIENTS WITH IBD TREATED WITH IL-4 ARE DEFECTIVE IN THEIR CAPACITY TO PROMOTE EPITHELIAL WOUND REPAIR IN VITRO
Bibliographic record
Abstract
We have shown that adoptive transfer of an IL-4 stimulated alternatively activated macrophage (AAM) (i.e. M(IL4)) can inhibit colitis in mice. Analyses of other mouse models of inflammation have shown that the AAM is important for wound healing: deletion of this macrophage can exacerbate disease by impairing wound repair. Extrapolating to IBD, we hypothesized that monocytes from patients with IBD, during active inflammation, would be impaired in their ability to convert to M(IL4)s and that this could contribute to impaired wound repair, thus promoting disease. To assess the ability of M(IL4)s to promote epithelial wound repair in an in vitro assay and determine if monocytes from patients with IBD can be converted to M(IL4)s with a wound repair capacity. Human blood-derived macrophages from healthy donors (HD) and patients with inflammatory bowel disease (Crohn’s disease active, n=4; Crohn’s disease inactive, n=7; ulcerative colitis active and inactive, both n=3) were exposed to IL-4 (10 ng/ml; 48h) or left unstimulated (controls). Expression of M(IL4) markers were assessed by qPCR (CD206, CD14, CCL18) or ELISA (CCL18). Confluent Caco2 epithelial cell monolayers were wounded with a razor blade and treated with supernatants from HD or IBD M(IL4)s and wound repair was measured (μm2) 48h later. TGFβ in M(IL4) supernatants was measured by ELISA, and the effect of adding anti-TGFβ antibodies to the wound repair assay tested. M(IL4)s from healthy donors showed increased expression of CD206 and CCL18, and reduced CD14. Supernatants from these M(IL4)s increased epithelial wound repair (36 ± 14%) (n=8, p<0.05) compared to baseline, had increased TGFβ (353 ± 78 pg/ml) compared to control macrophages (204 ± 71 pg/ml) (n=11, p<0.05), and were significantly inhibited in the ability to drive epithelial wound repair with addition of anti-TGFβ antibodies. Similarly, monocytes from patients with clinically inactive IBD converted to M(IL4)s with an ability to increase epithelial wound repair (32 ± 32%.). This was not observed with monocytes from patients with active disease that failed to induce CD206 expression or promote wound repair (2 ± 10%). Human M(IL4)s enhance epithelial wound repair, in part, via TGFβ. The inability of IL-4 treated macrophages to promote wound repair in individuals with active IBD suggests that a similar deficiency in vivo would contribute to lack of mucosal healing and ongoing inflammation. CCCNSERC Host-Parasites Interactions
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".