Expansion of Antigen-Specific Regulatory T Cells with the Topical Vitamin D Analog Calcipotriol
Bibliographic record
Abstract
1,25-Dihydroxyvitamin D(3) is immunosuppressive both in vivo and in vitro. Topical vitamin D analogs such as calcipotriol alter keratinocyte function, but their effects on cutaneous immune responses are less well understood. We demonstrate that exposure of the skin to calcipotriol before transcutaneous immunization with OVA protein and CpG adjuvant prevents Ag-specific CD8(+) T cell priming coincident with Langerhans cell depletion in the skin. Immunization through calcipotriol-treated skin induces CD4(+)CD25(+) regulatory T cells (Treg) that prevent subsequent Ag-specific CD8(+) T cell proliferation and IFN-gamma production. Treg induced by calcipotriol are able to inhibit the induction and the elicitation of protein contact hypersensitivity. Topical calcipotriol treatment also induces RANKL (receptor activator of NF-kappaB ligand) expression by keratinocytes, a TNF family member involved in modulation of skin dendritic cells. UV light B induces Ag-specific tolerance when it is applied before transcutaneous immunization. We suggest that UV light B-induced tolerance is induced via a vitamin D receptor-dependent mechanism as vitamin D receptor (VDR) knockout mice fail to increase FoxP3(+) Treg in their peripheral draining lymph node following irradiation. Additionally, keratinocytes of VDR(-/-) mice fail to induce RANKL upon UV irradiation or calcipotriol treatment. The in vivo expansion of Ag-specific Treg with the topical application of the vitamin D analog calcipotriol followed by transcutaneous immunization is a simple method to augment functional Ag-specific CD4(+)CD25(+)Foxp3(+) Treg populations and mimics Ag-specific UV-induced tolerance.
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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 | 0.000 |
| 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 | 0.001 |
| 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 | 0.000 |
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".