Mechanisms of CD154 release from T cells and subsequent biological activities (P3375)
Bibliographic record
Abstract
Abstract CD154 is a type II transmembrane protein critically involved in humoral immune responses. The soluble form of CD154 (sCD154) has been linked to various autoimmune and vascular disorders. Therefore, elucidating the mechanisms by which CD154 is release from the cell surface is of primordial importance. Using co-culture experiments, we show that CD154 is predominantly shed upon its engagement with CD40. Indeed, only CD40 and not α5β1 or αMβ2 is implicated in the cleavage of CD154 from Jurkat E6.1 T-cells. Interestingly, CD154 is cleaved independently of the formation of cell surface CD40 homodimers, a process previously shown to be involved in specific elements of CD154-induced signaling. We previously reported that the translocation of CD154 into lipid rafts is required for critical elements of CD154 signaling. Here, we show that CD154 is shed from the cell surface independently of this phenomenon. In contrast, we found that the protein kinase C signaling family and the metalloproteinases ADAM10 and ADAM17 are intimately involved in this process. Moreover, released sCD154 remains biologically active and can regulate critical biological responses such as activation of key survival signaling pathways and inhibition of cell death in α5β1 positive T-cells. In conclusion, our data add significant insights into the mechanisms by which CD154 is released and may explain the link between enhanced levels of sCD154 and T-cell survival and persistence during chronic inflammatory diseases.
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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 | 0.001 |
| 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".