PTH-061 The Proliferation of Human Intestinal Macrophage Subsets in IBD and Controls
Bibliographic record
Abstract
Introduction Inflammatory bowel disease (IBD) is thought to be dependent on cell populations of the mononuclear phagocyte (MNP) system; monocytes, macrophages and dendritic cells (DCs). However, it is not yet fully understood how these functionally different MNP populations contribute to IBD immunopathogenesis. To address this, it is necessary to identify the functional and phenotypic attributes of the different human intestinal MNP populations. Methods Fresh colonoscopic biopsies were taken, after signed informed consent, from patient with Crohn’s disease, ulcerative colitis and controls undergoing polyp surveillance scope. Biopsies were rapidly transferred to the lab for analysis. Using 12 parameter flow cytometry we have developed new strategies to identify and differentiate human intestinal MNPs, to enhance our understanding of their involvement in IBD. Results Within the colonic lamina propria, we unambiguously differentiate macrophage populations from dendritic cells (DCs: CD64− HLA-DR+ CD11c+; macrophages: CD64+ CD206+ HLA-DR+). The colonic macrophages homogeneously express CD33 and CD68, two previously reported markers of human macrophages. Furthermore, we demonstrate heterogeneous expression of CD14 within this macrophage population. Further characterisation of the colonic macrophages identified two distinct groups, identifiable by their differential expression of the mannose receptor, CD206. To address the characteristics of these macrophage populations we assessed their proliferation, by measuring Ki67 expression. Surprisingly, all populations were found to proliferate at higher than expected levels, both in the steady state and during inflammation. Conclusion We have developed novel protocols to isolate and identify MNP populations from human intestinal lamina propria. Human macrophages exhibit significant levels of proliferation under steady state conditions, and in samples from patients with IBD. Disclosure of Interest None Declared
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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 | 0.001 | 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) | 0.002 | 0.000 |
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".