Targeting Th17 Cells Through Inhibition of the Nuclear Receptor (NR) Retinoic Acid Receptor-Related Orphan Receptor γt (RORγt) in Highly Sensitized Renal Transplant Patients (HSP)
Bibliographic record
Abstract
🧾 Abstract Targeting Th17 cells through inhibition of the nuclear receptor (NR) retinoic acid receptor related orphan receptor γt (RORγt) in highly sensitized renal transplant patients (HSP) Ahmed Fouda1,2, Sarita Negi2, Steven Paraskevas1,2, Jean Tchervenkov1,2 1Department of Experimental Surgery, 2McGill University Health Center, McGill University, Montréal, Québec, Canada Introduction: Late and mixed rejections (LMR) are the most common causes of graft loss in transplantation. Currently there is no effective therapy for this condition. T helper 17 (Th17) cells play a major role in the initiation of LMR through the promotion of tertiary lymphoid tissue. Th17 activity is regulated by several transcription factors and by the NR RORγt. Our group has developed a novel class of molecules to target RORγt. We compared in-vitro Th17 polarization in HSP (cPRA=100%) vs non-sensitized renal transplant patients (NSP, cPRA=0%) and tested one of the novel compounds for their effect on cytokine production to validate their proposed effect. Methods: PBMCs from HSP (n=3), NSP (n=3), and healthy volunteers (HV, n=3) were polarized using CD3/CD28 beads, IL6, IL23, IL1β, and TGFβ for 14 days before adding RORγt inhibitor or vehicle for another 48 hours. Intracellular IL17A and IL21 were measured by flow cytometry. Results: Th17 polarization was higher in HSP compared to NSP or HV (fig1. p<0.05). RORγt inhibitor reduced IL17A and IL21 positive cells compared to controls (fig2. p<0.05). Conclusion: Targeting RORγt may be effective therapy in Th17 mediated LMR. This offers a novel potential targeted therapy for HSP after transplantation.📁 File DescriptionThe published version from the Canadian Transplant Summit 2019 Abstract Booklet (p. 90, Abstract ID 94) and the author preprint including the original figures are both provided.📍 Conference and MetadataPresented at: Canadian Transplant Summit (CST 2019) Presentation Date: 17 October 2019 Location: Banff, Alberta, Canada Abstract Category: Translational Research Presentation Type: Poster Presentation Authors: Ahmed Fouda, Sarita Negi, Steven Paraskevas, Jean Tchervenkov Affiliation: Department of Experimental Surgery, McGill University, Montreal, QC, Canada 📚 Full CitationFouda, A.; Negi, S.; Paraskevas, S.; Tchervenkov, J. Targeting Th17 Cells Through Inhibition of the Nuclear Receptor (NR) Retinoic Acid Receptor-Related Orphan Receptor γt (RORγt) in Highly Sensitized Renal Transplant Patients (HSP). In Proc. Can. Transplant Summit 2019; p. 90 (Abstr. 94). Canadian Transplant Summit (CST 2019), Montréal, QC, Canada, 16–19 October 2019. DOI: 10.6084/m9.figshare.30434146 © 2019, Ahmed Fouda.
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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) | 0.001 | 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".