The synovial lining macrophage layer develops in the first weeks of life in a CSF1- and TGFβ-dependent but monocyte-independent process
Bibliographic record
Abstract
Summary Synovial joints harbor a protective lining layer, consisting of fibroblasts and macrophages, which form an epithelial-like barrier. In inflamed joints, lining macrophages regulate both early inflammatory cell influx and resolution. Despite these critical functions, it is currently unknown at what stage during development the synovial macrophage lining is established, and which signals drive this process. Here, we use a combination of genetic models and in vivo perturbations, single cell transcriptomics and imaging to delineate the process of lining formation in mice. We find that the synovial lining is immature at birth and becomes established within the first 3 weeks of life. In this window, the lining is gradually populated with macrophages that originate from fetal sources, proliferate and acquire the lining-specific transcriptional identity. In contrast, monocytes contribute only minimally to the developing lining, and their input remains limited in healthy adulthood. We identify CSF1 and TGFβ as key signals in this process, which also involves mechanosensing through PIEZO1. Our study thus identifies the early postnatal window as a critical period for lining macrophage development, with potential lifelong impact on joint health and disease.
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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) | 0.002 | 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".