Bibliographic record
Abstract
Introduction: The molecular basis of lymphocyte trafficking to the liver via the unique sinusoidal vascular bed is poorly understood.Classical adhesion receptors such as selectins play a minimal role in the sinusoids leading us to look for novel receptors.C-type lectin-like receptors (LLRs) are responsible for a wide range of functions related to innate and adaptive immunity.Two receptors within this family, mannose receptor (MR) and CLEVER-1, are expressed on lymphatic endothelium where they mediate lymphocyte adhesion and transmigration.Aim: Because hepatic sinusoidal endothelium has a similar phenotype to lymphatic endothelium we hypothesised that these receptors will be involved in lymphocyte trafficking to the liver via the sinusoidal vascular bed.Methods: We used immunohistochemistry and immunofluorescence microscopy to analyse the distribution of MR and CLEVER-1 in normal and inflamed human liver tissue.Cell-specific expression was confirmed using RT-PCR on isolated primary human sinusoidal endothelial cells (HSEC) and compared with other non-hepatic endothelial cells.Lymphocyte adhesion and transendothelial migration was assessed using function blocking antibodies in static adhesion assays on frozen liver sections and flow based adhesion assays with HSEC.Results: Both MR and CLEVER-1 were detected within sinusoids in normal liver.Costaining localised the receptors to kupffer cells and to HSEC.Staining varied across the hepatic lobule but we noted that the intensity of both receptors on sinusoidal cells increased in chronic liver disease compared with normal liver.RT-PCR confirmed mRNA expression in isolated primary HSEC.Adhesion assays using human peripheral lymphocytes demonstrated that CLEVER-1 on HSEC can support lymphocyte adhesion.Conclusions: MR and CLEVER-1 are expressed on hepatic sinusoids where they support lymphocyte adhesion.The increased expression seen in chronic inflammatory liver disease suggests an important role in lymphocyte recruitment in chronic inflammatory liver disease.LLRs should be added to the list of unconventional adhesion proteins that support lymphocyte adhesion within the liver and may be targets for anti-inflammatory therapy in chronic liver disease.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.766 | 0.677 |
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; the direct Gemma label and the distilled Codex classifier agree on what is shown here.
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".