Semaphorin‐3E attenuates intestinal inflammation through the regulation of the communication between splenic CD11C<sup>+</sup> and CD4<sup>+</sup>CD25<sup>−</sup> T‐cells
Bibliographic record
Abstract
Background and Purpose An alteration in the communication between the innate and adaptive immune cells is a hallmark of ulcerative colitis (UC). Semaphorin‐3E (SEMA3E), a secreted guidance protein, regulates various immune responses. Experimental Approach We investigated the expression of SEMA3E in colonic biopsies of active UC patients and its mechanisms in Sema3e −/− mice using an experimental model of UC. Key Results SEMA3E level was decreased in active UC patients and negatively correlated with pro‐inflammatory mediators. Colonic expression of SEMA3E was reduced in colitic Sema3e +/+ mice, and recombinant (rec‐) Plexin‐D1 treatment exacerbated disease severity. In vivo rec‐SEMA3E treatment restored SEMA3E level in colitic Sema3e +/+ mice. In Sema3e −/− mice, disease severity was increased, and rec‐SEMA3E ameliorated these effects. Lack of Sema3e increased the expression of CD11c and CD86 markers. Colitic Sema3e −/− splenocytes and splenic CD11c + cells produced more IL‐12/23 and IFN‐γ compared to Sema3e +/+ , and rec‐SEMA3E reduced their release as much as NF‐κB inhibitors, whereas an NF‐κB activator increased their production and attenuated the effect of rec‐SEMA3E. Colitic Sema3e −/− splenic CD11c + /CD4 + CD25 − T‐cell co‐cultures produced higher concentrations of IFN‐γ and IL‐17 when compared to colitic Sema3e +/+ splenic cell co‐cultures, and rec‐SEMA3E decreased these effects. In vitro, anti‐IL‐12p19 and ‐12p35 antibodies and rec‐IL‐12 and ‐23 treatment confirmed the crosstalk between CD11c + and CD4 + CD25 − T‐cells. Conclusion and Implications SEMA3E is reduced in colitis and modulates colonic inflammation by regulating the interaction between CD11c + and CD4 + CD25 − T‐cells via an NF‐κB‐dependent mechanism. Thus, SEMA3E could be a potential therapeutic target for UC patients.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".