Differential regulatory mechanisms underlie the control of Vγ4 and Vγ6 γδT17 development by HEB transcription factors
Bibliographic record
Abstract
Abstract IL-17-producing γδ T-cells (γδT17) are critical components of the innate immune system, but the pathways that control their development are not well understood. We have previously shown that HEB transcription factors operate upstream of Sox4 and Sox13 to initiate the γδT17 program. However, the defects in fetal Vγ4+ γδT17 cells appear to be distinct from those in the Vγ6+ γδT17 cells. In the absence of HEB, fetal Vγ4+ γδT17 cells are unable to develop, whereas Vγ6+ γδT17 cells develop but are not able to produce IL-17. To further understand the molecular mechanisms that underlie these defects, we performed single cell RNA-seq on E18.5 γδTCR+ cells from WT and HEB-deficient mice, and did differential gene expression analysis on clusters expressing Vγ5, Vγ6, or Vγ4 mRNA. Our analysis revealed that in addition to Sox4 and Sox13, an entire suite of genes associated with the development and function of γδT17 cells was downregulated in HEB-deficient cells. Furthermore, Vδ4, which is normally restricted to cells expressing Vγ6 or Vγ5, was expressed at high levels in nearly all clusters, whereas the levels of Vγ4 and Vδ5 mRNA were severely decreased. These results suggest that direct control of Vγ and Vδ chain mRNA expression underlie the defect in Vγ4+ cell development, whereas Vγ6+ cells require a direct input from HEB into the gene program controlling γδT17 differentiation even in the presence of proper γδTCR pairing.
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| 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".