CD4+ T cell-derived Interleukin-21 is required for the efficient clearance of <i>Citrobacter rodentium</i> (MUC5P.744)
Bibliographic record
Abstract
Abstract Interleukin-21 (IL-21) is critical for host defense against infections with intracellular and extracellular pathogens. Although most infections occur following an initial colonization at mucosal surfaces, no studies have addressed the role of IL-21 in controlling bacterial colonization and dissemination from the colon. Using a novel Il21fl/fl reporter and CD4-Cre conditional knockout mouse, we show that IL-21+CD4+ T cells are the dominant source of IL-21 required for the efficient clearance of the enteric bacterial pathogen Citrobacter rodentium. Consistent with the complete Il21-/- mice, we found that mice with a conditional deletion of Il21 from CD4+ T cells had a greater incidence and severity of colitis, increased bacterial dissemination to the spleen and liver, reductions in IFN-γ+IL-17A- CD4+ T cells, and a decreased ratio of CXCR5+PD-1+ T follicular helper (Tfh) to FoxP3+ T follicular regulatory cells (Tfr) following infection. In association with impaired T cell differentiation, we found that conditional deletion of Il21 from CD4+ T cells lead to a reduction in the number of plasma cells and a reduction in C. rodentium-specific IgG. Finally, using bone marrow chimeric mice, we found that B cells and T cells require IL-21R expression to mediate the clearance of C. rodentium. These findings establish that IL-21-producing CD4+T cells can inhibit the dissemination of enteric bacterial pathogens and enhance their clearance from the site of infection via humoral immunity.
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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) | 0.002 | 0.001 |
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".