Increased Prevalence of Circulating Novel IL-17 Secreting Foxp3 Expressing CD4+ T Cells and Defective Suppressive Function of Circulating Foxp3+ Regulatory Cells Support Plasticity Between Th17 and Regulatory T Cells in Inflammatory Bowel Disease Patients
Why this work is in the frame
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Bibliographic record
Abstract
BACKGROUND: IL-17 and Foxp3 double-expressing (DE) CD4(+) T lymphocytes are novel crossover immune cell population, but the presence and role of these cells in human intestinal inflammation is unclear. The aim of this study was to investigate the circulating IL-17 and Foxp3 DE CD4(+) T lymphocytes in patients with inflammatory bowel disease (IBD). METHODS: The entire cohort consisted of 79 subjects: 31 patients with Crohn's disease, 28 patients with ulcerative colitis, and 20 healthy control subjects (HC). IBD patients with evidence of active disease at endoscopy were entered into the study. Peripheral blood mononuclear cells were used for ex vivo and in vitro studies to assess the characteristics and generation of these novel cells and the function of circulating Foxp3 CD4(+) regulatory T lymphocytes (Treg) in patients with IBD compared with HC. RESULTS: Patients with IBD had significantly higher prevalence of IL-17 and Foxp3 DE CD4(+) T lymphocytes compared with age- and gender-matched HC. These cells expressed RORγt. The ability of Treg cells to suppress autologous T-cell proliferation was reduced by approximately 60% in patients with IBD compared with HC. Increased generation of these DE cells was demonstrated by the modulation of cytokine environment of CD4(+) lymphocytes in vitro in patients with Crohn's disease. CONCLUSIONS: Prevalence of circulating IL-17 and Foxp3 DE CD4(+) T cells is increased in patients with IBD. Coexpression of RORγt and Foxp3 in these cells implies conversion from Treg cells to Th17 cells. This is associated with a decreased suppressive function of Foxp3 CD4(+) T lymphocytes in patients with IBD.
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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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| 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 it