Proinflammatory CX3CR1+CD59+Tumor Necrosis Factor–Like Molecule 1A+Interleukin‐23+ Monocytes Are Expanded in Patients With Ankylosing Spondylitis and Modulate Innate Lymphoid Cell 3 Immune Functions
Bibliographic record
Abstract
Objective Gut‐derived innate lymphoid cell 3 ( ILC 3) has been shown to participate in the pathogenesis of ankylosing spondylitis ( AS ). CX 3 CR 1+ mononuclear phagocytes ( MNP s) have been demonstrated to modulate ILC 3 function in the gut. This study was undertaken to investigate the role of proinflammatory CX 3 CR 1+ CD 59+ MNP s in modulating ILC 3 function in AS patients. Methods MNP subsets in the blood of AS patients and controls were analyzed by flow cytometry. The presence of CX 3 CR 1+ CD 59+ cells in tissue was confirmed by confocal microscopy. Expression of the proinflammatory chemokines CX 3 CL 1 and CCL 2 and decoy receptor 6 (DcR‐6) was analyzed. Peripheral CX 3 CR 1+ CD 59+ cells were cocultured with ILC 3, and changes in their frequency were evaluated by flow cytometry. Transcriptome analysis of circulating CX 3 CR 1+ monocytes was also performed. Results DcR‐6 deficiency and CCL 2 overexpression were observed in inflamed tissues from AS patients. In the gut, the proinflammatory CX 3 CR 1+ CD 59+ MNP population was expanded, correlated with the presence of bacteria, and produced high levels of tumor necrosis factor–like molecule 1A ( TL 1A) and interleukin‐23 ( IL ‐23). MNP s positive for CD 11b, CD 11c, and major histocompatibility complex class II , predominantly expressing CX 3 CR 1, were also expanded in the small intestines of treatment‐naive SKG relative to BALB /c mice. The frequency of gut‐derived CX 3 CR 1+ CD 59+ CCR 9+ TL 1A+ IL ‐23+ MNP s was significantly higher in the peripheral blood and synovial fluid of AS patients than controls. CCR 9+ CX 3 CR 1+ CD 59+ monocytes were also expanded in AS synovial and bone marrow samples. Transcriptome analysis of isolated CX 3 CR 1+ CD 59+ monocytes demonstrated a specific proinflammatory profile in AS . Isolated proinflammatory CX 3 CR 1+ CD 59+ MNP s from AS patients induced the expansion and activation of ILC 3. Conclusion Proinflammatory CX 3 CR 1+ CD 59+ TL 1A+ IL ‐23+ MNP s are expanded in AS patients and display a specific proinflammatory transcriptome profile. Given the ability of these cells to support ILC 3 expansion, they may promote a sustained proinflammatory status in AS .
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".