Circulating fibrocytes contribute to the pathogenesis of collagen antibody–induced arthritis
Bibliographic record
Abstract
OBJECTIVE: Rheumatoid arthritis (RA) is a systemic autoimmune disease resulting in joint inflammation. Fibroblast-like synoviocytes in affected joints are responsible for pannus formation and cytokine/chemokine production, resulting in leukocyte recruitment and bone/cartilage destruction. Previously, we identified a multipotent stem cell population of activated fibrocytes in the blood of patients with RA that may have a role in disease pathogenesis, perhaps as fibroblast-like synoviocyte precursors. The aim of this study was to further characterize the contribution of circulating fibrocytes to the pathogenesis of RA. METHODS: Circulating fibrocytes were isolated from mice with collagen-induced arthritis and transferred intravenously into recipient mice with collagen antibody-induced arthritis (CAIA). The activation status of circulating fibrocytes was determined using multidimensional phosphoflow cytometric analysis of the signaling effectors STAT-5, STAT-1, AKT, and JNK. Circulating fibrocyte trafficking and matrix metalloproteinase (MMP) activity were assessed in real time using fluorescence molecular tomography, specifically labeling circulating fibrocytes with CellVue Maroon and measuring MMP activity using MMPSense 680. RESULTS: The numbers of circulating fibrocytes were increased early during the onset of CAIA, concomitant with their activation, as measured by phosphorylation of STAT-5. Adoptive transfer of circulating fibrocytes augmented disease scores and increased class II major histocompatibility complex expression and peripheral blood phosphoactivation profiles in recipient mice with CAIA. Notably, adoptively transferred fluorescence-labeled circulating fibrocytes rapidly migrated into the affected joints of recipient mice with CAIA, and this was associated with augmented neutrophil recruitment into affected joints and MMP activation. CONCLUSION: Circulating fibrocytes migrate to joints and influence the onset of disease processes in arthritis.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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 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".