PMO-118 The effects of th17 cytokines on liver parenchymal cells shape the microenvironment for local generation of TH17/TC17 in inflammatory liver disease
Bibliographic record
Abstract
Introduction IL-17 secreting T cells have been implicated in autoimmunity, inflammatory disease and provide a link between the innate and adaptive immune responses. High numbers of IL-17-producing T cells which also secrete IL-21 and IL-22 are found in close proximity to bile ducts in several liver diseases. T h17 related cytokines have multiple effects and may be involved in both effector responses and repair and regeneration. Methods Primary human parenchymal cells were assessed for cytokine receptor expression by western blotting. The effects of stimulation with recombinant IL-17, IL-21, IL-22, TNFa or IFN-g alone or in combination were compared for apoptosis using annexin staining, proliferation was measured by in situ Ki67 staining and adhesion molecule expression was assessed by flow cytometry. Secretion of IL-1b, IL-6, IL-23 and TGF-b1 was assessed by ELISA. Results All parenchymal cells expressed IL-17R, IL-21R and IL-22R. T h17 related cytokines did not cause apoptosis but led to parenchymal cell proliferation. Cholangiocytes and hepatocytes responded best to IL-17, whereas sinusoidal endothelial cells were responsive to IL-22. Endothelial cells upregulated adhesion molecules in response to T h17 related cytokines. Cholangiocytes responded to T h17 cytokines by secreting high levels of IL-1b, IL-6, IL-23 and TGF-b1 all cytokines that support the survival of T h17 and T c17 cells. Conclusion Liver parenchymal cells express IL-17, IL-21 and IL-22 receptors and proliferate in response to T h17 cytokines. Upregulation of adhesion molecules by sinusoidal endothelial cells promotes lymphocyte recruitment and retention. Cholangiocytes also respond by secreting T h17 /T c17 polarising cytokines. Therefore T h17 related cytokines secreted by infiltrating lymphocytes may activate the epitheliome to generate a local environment characterised by cholangiocyte proliferation and T h17 /T c17 cell survival, thus contributing to bile duct proliferation and persistent chronic inflammation that characterises many liver diseases. Competing interests None declared.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".