17β-Estradiol suppresses MHC class I chain-related B gene expression via an intact GC box
Bibliographic record
Abstract
Major histocompatibility complex class I chain-related B (MICB) is a membrane-bound glycoprotein involved in both innate and adaptive immunity through its interaction with NKG2D receptors present on γδ T, αβ CD8(+) T, and natural killer cells. Factors known to upregulate MICB expression include heat shock, viral or bacterial infection, and tumorigenesis, and here, we explored the effect of 17β-estradiol (E2) on MICB regulation. Physiological concentrations of E2 were found to suppress MICB mRNA and surface protein levels and this effect was antagonized by the antiestrogen ICI 182780. The inhibitory effect of E2 was also observed for other NKG2D ligands, MICA and ULBPs. Evaluation of promoter fragments from the common MICB*00502 allele revealed that inhibition of transcription by E2 required the GC box at -87. The electrophoretic mobility shift assay and supershift analysis established the presence of SP1, SP3, or estrogen receptor α recognition sites within the MICB promoter sequence and interaction of these factors in situ was confirmed by chromatin immunoprecipitation. We conclude that E2 upon forming a complex with its cognate receptor suppresses MICB expression through binding with SP1/SP3 sites within the MICB promoter GC box. These results suggest that the partial benefit of 17β-estradiol on autoimmune diseases may be mediated by reducing the immune NKG2D ligands like MICB.
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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) | 0.000 | 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) | 0.001 | 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 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".