Alleviating graft-versus-host disease by directing regulatory T cells to the gut … It is all about location, location, location
Bibliographic record
Abstract
Adoptive transfer of regulatory T cells (Tregs) is an exciting and promising strategy for suppressing undesired immune responses during transplantation. Preclinical and clinical studies have demonstrated the ability of unmodified polyclonal Tregs to inhibit the development of graft-versus-host disease (GVHD) in the setting of allogeneic hematopoietic stem cell transplantation; however, an outstanding question was whether the efficacy of this approach could be improved by promoting Treg trafficking to sites of inflammation. Intestinal inflammation is a major driver of acute GVHD, and there is a correlation between intestinal GVHD and lower proportions of blood Tregs expressing the gut-homing integrin α4β7. 1 Engelhardt B.G. Jagasia M. Savani B.N. et al. Regulatory T cell expression of CLA or α4β7 and skin or gut acute GVHD outcomes. Bone Marrow Transplant. 2011; 46: 436-442 Crossref PubMed Scopus (37) Google Scholar Moreover, Tregs from patients with Crohn’s disease express lower levels of α4β7. 2 Goldberg R. Scotta C. Cooper D. et al. Correction of defective T-regulatory cells from patients with Crohn’s disease by ex vivo ligation of retinoic acid receptor-α. Gastroenterology. 2019; 156: 1775-1787 Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar Thus, directing therapeutic Tregs to the gut may enhance the ability of these cells to alleviate intestinal inflammation. Enforced gut homing of murine regulatory T cells reduces early graft-versus-host disease severityAmerican Journal of TransplantationVol. 23Issue 8PreviewDamage to the gastrointestinal tract following allogeneic hematopoietic stem cell transplantation is a significant contributor to the severity and perpetuation of graft-versus-host disease. In preclinical models and clinical trials, we showed that infusing high numbers of regulatory T cells reduces graft-versus-host disease incidence. Despite no change in in vitro suppressive function, transfer of ex vivo expanded regulatory T cells transduced to overexpress G protein–coupled receptor 15 or C-C motif chemokine receptor 9, specific homing receptors for colon or small intestine, respectively, lessened graft-versus-host disease severity in mice. Full-Text PDF
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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 | 0.006 | 0.012 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.003 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.002 | 0.002 |
| Scholarly communication | 0.006 | 0.004 |
| Open science | 0.003 | 0.001 |
| Research integrity | 0.012 | 0.025 |
| Insufficient payload (model declined to judge) | 0.009 | 0.006 |
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".