Modulation of Id3 induces a fetal-specific HEB-dependent gamma delta T cell developmental pathway in the adult mouse thymus
Bibliographic record
Abstract
Abstract Gamma delta T cells (γδ T cells) are key players in tissue barrier homeostasis and immunity. Understanding the molecular mechanisms by which γδ T cells are programmed to develop into the γδT17 lineage is essential to develop strategies for controlling IL-17 activity during pathogenic conditions. Previously we showed that the E protein transcription factor HEB is an essential regulator of the γδT17 lineage, and that the generation of fetal γδT17 cells occurs through a HEB-dependent fetal-restricted pathway that does not involve upregulation of CD73 (Pathway 2). Id3, an antagonist of E proteins, inhibits key regulators of γδT17 development. Therefore, we hypothesized that the loss of Id3 would enhance γδT17 development. We characterized adult Id3-RFP knock-in mice, and found that the Id3−/− recapitulated the previously established expansion of Vγ1+ γδ T cells. However, the adult Id3+/− thymus showed a re-emergence of Pathway 2, suggesting that reduced Id3 levels promotes the fetal HEB-dependent γδT17 program. Moreover, there was an increase in Vγ1-Vγ4- γδ T cells, which suggests the appearance of Vγ6+ cells that are normally restricted to the fetal thymus. Interestingly, Vγ4+ cells and Vγ1-Vγ4-cells in Id3+/− mice displayed Pathway 2 profiles, while Vγ1+ cells exhibited the normal adult thymic developmental profile leading to mature CD73+ γδ T cells in both Id3+/− and Id3−/− mice. Future studies will examine whether reduced HEB in the Id3+/− mice inhibits Pathway 2 in the adult thymus, and obtain more definitive evidence as to whether the Id3+/− γδ T cells in the adult thymus develop toward the IL-17 fate. In conclusion, our studies indicate that the balance between E proteins and Id3 regulates the developmental programming pathway of γδ T cells.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".