Endogenous Calcitriol Synthesis Controls the Humoral IgE Response in Mice
Bibliographic record
Abstract
Abstract The vitamin D receptor participates in the control of IgE class-switch recombination in B cells. The physiologic vitamin D receptor agonist, 1,25(OH)2D3 (calcitriol), is synthesized by the essential enzyme 25-hydroxyvitamin D3-1α-hydroxylase (CYP27B1), which can be expressed by activated immune cells. The role of endogenous calcitriol synthesis for the regulation of IgE has not been proven. In this study, we investigated IgE-responses in Cyp27b1-knockout (KO) mice following sensitization to OVA or intestinal infection with Heligmosomoides polygyrus. Specific Igs and plasmablasts were determined by ELISA and ELISpot, Cyp27b1 expression was measured by quantitative PCR. The data show elevated specific IgE and IgG1 concentrations in the blood of OVA-sensitized Cyp27b1-KO mice compared with wild-type littermates (+898 and +219%). Accordingly, more OVA-specific IgG1-secreting cells are present in spleen and fewer in the bone marrow of Cyp27b1-KO mice. Ag-specific mechanisms are suggested as the leucopoiesis is in general unchanged and activated murine B and T lymphocytes express Cyp27b1. Accordingly, elevated specific IgE concentrations in the blood of sensitized T cell–specific Cyp27b1-KO mice support a lymphocyte-driven mechanism. In an independent IgE-inducing model, i.e., intestinal infection with H. polygyrus, we validated the increase of total and specific IgE concentrations of Cyp27b1-KO compared with wild-type mice, but not those of IgG1 or IgA. We conclude that endogenous calcitriol has an impact on the regulation of IgE in vivo. Our data provide genetic evidence supporting previous preclinical and clinical findings and suggest that vitamin D deficiency not only promotes bone diseases but also type I sensitization.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 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".