CXCR3 blockade impedes the development of Sjögren’s syndrome-like xerostomia in non-obese diabetic mice
Bibliographic record
Abstract
Abstract The chemokine receptor CXCR3 plays an important role in T cell recruitment in various immune responses and autoimmune diseases. Expression of CXCR3 ligands, including CXCL9, CXCL10 and CXCL11, is elevated in the salivary glands of patients with Sjögren’s syndrome (SS). To elucidate whether interaction between CXCR3 and its ligands is required for the development of SS, we administrated an anti-CXCR3 blocking antibody to non-obese diabetic (NOD) mice, a well-defined model of SS, during the stage prior to disease onset. CXCR3 blockade significantly improved salivary secretion, indicating a remission of SS clinical manifestation. CXCR3 blockade did not affect the gross leukocyte infiltration of the submandibular glands (SMG) as assessed by H&E staining. However, flow cytometric analysis showed that anti-CXCR3 treatment markedly reduced the percentage of CXCR3+CD8 T cells and CD44+CD8 T cells, without affecting that of CXCR3+CD4 T cells and CD44+CD4 T cells in the SMG and submandibular lymph nodes, suggesting a selective effect of CXCR3 blockade on effector T cytotoxic 1 cells. Meanwhile, SMG expression of inflammatory factor TNF-α was markedly diminished by anti-CXCR3 treatment. Consistent with this, CXCR3 blockade significantly enhanced SMG expression of tight junction protein claudin-1 and water channel protein aquaporin-5, two factors that are crucially required for normal salivary secretion and can be down-regulated by TNF-α. Taken together, our findings demonstrated that the interaction between endogenous CXCR3 and its ligands plays a proinflammatory and pathogenic role in the development of SS-like xerostomia in NOD mouse model.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| 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 | 0.001 | 0.002 |
| 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".