CD40 Ligand and Its Receptors in Atherothrombosis
Bibliographic record
Abstract
Atherothrombosis 80 2. The CD40L system 2.1 CD40L CD40L, also known as CD154, is a 39 kDa transmembrane protein belonging to the tumor necrosis factor (TNF) superfamily originally identified on cells of the immune system. 12,13 e interaction of CD40L with its respective receptor on B cells, CD40, a glycoprotein also from the TNF receptor (TNFR) family, is of critical importance for immunoglobulin isotype switching during the immune response. 14The importance of this interaction is highlighted by the pathophysiological manifestations seen in patients suffering from the X-linked hyperimmunoglobulin-M syndrome, in which B-cells fail to produce the immunoglobulin's IgG, IgA and IgE as a consequence of a genetic mutation in the CD40L gene. 15Because of its wide distribution across cells of the vascular system (endothelium, B and T lymphocytes, neutrophils, platelets, monocytes, dentritic cells and smooth muscle cells), the CD40L/CD40 dyad also shares important implications in cell-mediated immunity.7][18][19] These cellular events are also the main mechanisms by which CD40L regulates numerous inflammatory disorders, in particular atherothrombosis and its related complications.[22] CD40L receptors CD40CD40 is the classical high affinity receptor for CD40L.It is constitutively or inducibly expressed by most cells of the vascular system (hematopoietic and non-hematopoietic cells) and represents the main signaling molecule in the CD40L/CD40 receptor-ligand pair. 23The cytoplasmic domain of CD40 bears signaling domains required for the association of binding proteins termed TNF receptor-associated factors (TRAFs). 24During humoral immunity, a tight interplay between dendritic cells, T-lymphocytes and B-lymphocytes occurs, throughout which the activation of CD40 provides a crucial signal for the activation, differentiation and secretion of immunoglobulins by B cells. 25 Moreover, CD40 activation in these cells induces an important anti-apoptotic signal that facilitates cell survival and differentiation, primarily through activation of the anti-apoptotic proteins Bcl-XL, A20, Bfl-1 and Mcl-1, which protect against Fas ligand and TNF-induced cell death. 26As discussed above, CD40 signaling plays a significant role in cell-mediated immunity, an important aspect by which the CD40L/CD40 dyad initiates and exacerbates atherosclerotic lesions.For instance, CD40 activation on endothelial cells induces the up-regulation of a plethora of proinflammatory adhesion molecules, cytokines, chemokines, matrix metalloproteinases and procoagulants. 16In addition, it has been demonstrated that upon CD40L binding CD40 activation on platelets can enhance platelet function and promote the secretion of inflammatory cytokines involved in plaque formation (this aspect will be discussed in greater detail bellow).
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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 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.014 | 0.010 |
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".