Ectodomain Shedding of FLT3 Ligand Is Mediated by TNF-α Converting Enzyme
Bibliographic record
Abstract
FLT3 ligand (FLT3L) has diverse roles in the hematopoietic system, which include stimulating proliferation of hematopoietic precursors and development of NK cells and dendritic cells. FLT3L is initially synthesized as a membrane-bound protein, which must be cleaved to become a soluble growth factor. However, little is known about the enzyme involved in the proteolytic release of FLT3L. In the current study, we show that shedding of FLT3L is metalloprotease-dependent, and that this proteolytic activity was abolished in fibroblasts lacking TNF-alpha converting enzyme (TACE) and could be rescued by reintroducing wild-type TACE in these cells. Moreover, we found that cells derived from the thymus of conditional TACE-deficient mice produce less FLT3L, and that serum FLT3L levels in these TACE mutant mice are significantly lower, both after LPS treatment and in the absence of such a challenge, further corroborating the relevance of TACE as FLT3L sheddase in vivo. Considering the involvements of FLT3 and FLT3L in hematopoietic malignancies and stem cell mobilization, the identification of the enzyme involved in FLT3L shedding may have important clinical implications.
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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".