Pathogenic role of plasmacytoid dendritic cells in the development and onset of Sjögren’s syndrome-like exocrinopathy in non-obese diabetic mice
Bibliographic record
Abstract
Abstract Plasmacytoid dendritic cells (pDCs), which are the most potent producers of type I IFNs, have been demonstrated to be critically involved in the induction of multiple autoimmune diseases. In Sjögren’s syndrome (SS), the presence of pDCs and activated type I IFN pathways has been shown in the salivary glands of patients, and the disease severity closely correlates with type I IFN activity. However, the particular role of pDCs in the pathogenesis of SS remains unknown. To investigate whether pDCs play a crucial role in the development and onset of SS, we administrated a pDC-depleting anti-BST2 antibody to female non-obese diabetic (NOD) mice, a spontaneous model of SS during the early stage of SS development, from 4 to 7 weeks of age. Mice were analyzed at 10 weeks of age around the clinical onset of the disease. Anti-BST2 treated mice had significantly higher salivary flow rate than IgG-treated control group, indicating the remission of SS-like xerostomia by pDC depletion. Meanwhile, anti-BST2 treatment inhibited leukocyte infiltration of submandibular glands (SMGs), as demonstrated by H&E staining. Consistent with these results, flow cytometric analysis provided evidence that administration of anti-BST2 not only lowered the frequency of total leukocytes, CD4 T cells, CD8 T cells, B cells and pDCs, but also reduced the proportion of CD44+CD4 T cells, CD44+CD8 T cells and CD86+B cells among the total SMG cells of NOD mice. These changes were accompanied by downregulation of CD40, CD40L, Lt-α, Lt-β, TNF-α, IFN-γ, CXCL9, CXCL11 and NOS2, as determined by RT2 Profiler PCR array, suggesting an attenuation of SMG inflammation. Taken together, pDC depletion at the early stage of disease development hinders the pathogenesis of SS-like exocrinopathy.
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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) | 0.000 | 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) | 0.000 | 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".