Context dependent differentiation of resident and inflammatory intestinal macrophages from a common monocyte precursor (120.1)
Bibliographic record
Abstract
Abstract Macrophages (mϕ) are essential for homeostasis and protective immunity in the intestine, but also drive pathology in inflammatory bowel disease. It is not clear whether these different functions are due to distinct populations of mϕ, or if the same cell change. We show here that two populations of mϕ exist within the mouse colon, based on the levels of CX3CR1 expression. Most resting mϕ express CX3CR1 at much higher levels than any other tissue mϕ and also express CD11c. These resident mϕ produce a balanced mixture of TNFα and IL10 constitutively, but respond poorly to stimulation via TLR, despite expressing all TLR. During acute DSS colitis, mϕ expressing lower levels of CX3CR1 come to dominate. These “inflammatory” mϕ produce TNFα predominantly and respond via TLR. Using a combination of gene profiling, immunophenotyping and adoptive transfer models, we show that CX3CR1int mϕ in both healthy and inflamed intestine are derived from Ly6Chi CCR2+ monocytes that upregulate CX3CR1 after entering the intestine, sequentially acquiring F4/80 and class II MHC expression. Under resting but not inflammatory conditions, the newly arrived monocytes differentiate further, becoming CX3CR1hi, producing IL10, expressing CD163 and CD206 and becoming TLR unresponsive. These results provide novel evidence that “resident” and “inflammatory” mϕ in the intestine derive from the same monocyte precursor whose ultimate fate is determined locally and depends on the presence or absence of inflammation
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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) | 0.001 | 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".