Proinflammatory macrophages transporting gut-derived bacterial DNA drive autoimmune arthritis in spondyloarthropathy
Bibliographic record
Abstract
Spondyloarthritis (SpA) is an inflammatory arthritis of the spine and joints associated with intestinal inflammation, in which it is hypothesized that innate immune exposure to enteroinvasive species is followed by self-/bacterial peptide presentation. However, the mechanisms underlying loss of tolerance to gut bacteria in genetically at-risk individuals are unclear. Curdlan-treated (β-1,3-glucan, dectin-1 ligand-treated) ZAP-70W163C (SKG) mice develop autoimmune arthritis and ileitis associated with Gram-negative fecal dysbiosis. Using gnotobiotic mice, we show that curdlan-treated SKG mice monoassociated with Parabacteroides goldsteinii or Lactobacillus murinus developed ileitis, arthritis, and enthesitis, while BALB/c mice were tolerant. Gnotobiotic SKG ileum upregulated Il23a and ER stress genes and lost goblet cells. Whereas bacterial DNA colocalized with neutrophils and inflammatory macrophages in SKG lamina propria, periarticular bone marrow, entheses, and spleen, in BALB/c mice, bacterial DNA colocalized with resident macrophages in lamina propria and spleen. Human psoriatic-arthritis synovial tissue also contained cell-associated perivascular bacterial DNA. Curdlan-treated SKG spleen/bone marrow macrophages transferred severe arthritis and expanded Th17 cells in naive SKG recipients, while BALB/c or germ-free SKG macrophages transferred mild arthritis and regulated Th17 cells. Thus, bacterial DNA and myeloid cells in the gut and their subsequent traffic regulate or enforce T cell pathogenicity in SpA.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".