Vitamin D receptor restricts T helper 2-biased inflammation in the heart
Bibliographic record
Abstract
Background and aims: The aberrant immune responses play a critical role in the pathogenesis of myocarditis. Vitamin D receptor (VDR) has immune regulatory functions. This study aims to investigate the role of VDR in restricting the immune inflammation in the heart. Methods and results: The human heart samples were obtained from the heart transplantation. T helper (Th)2 and Th1 responses in the heart tissue were characterized by histology and immune assay. VDR-/- mice and recombination activating gene 2-/- mice were used in the experiments to test the role of VDR in maintaining the homeostasis in the heart. The results showed that, besides tissue damage, lower expression of VDR, high frequency of Th2 cells and increase in Th2 cytokines in the hearts of patients with myocarditis at the end stage of heart failure. The spontaneous Th2-biased inflammation was observed in the hearts of VDR-/- mice. CD4+ T cells from the VDR-/- mouse hearts were at highly activating status. The naïve VDR-/- CD4+ T cells and naïve CD4+ T cells from human hearts with myocarditis were prone to differentiate into Th2 cells. VDR formed complexes with GATA3, the interleukin (IL)-4 transcription factor, to prevent the Il4 gene transcription. Transplantation with VDR-/-CD4+ T cells induced the Th2-biased inflammation in the hearts of Rag2-/- mice. Reconstitution of VDR in CD4+ T cells inhibited the Th2-biased inflammation in the heart. Conclusions: VDR-deficiency contributes to the pathogenesis of myocarditis. To enhance the VDR expression in CD4+, T cells haves the therapeutic potential for the treatment of myocarditis.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.013 | 0.006 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 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".