Semaphorin3E is a novel regulator of IgE through regulation of germinal center responses in a mouse model of allergic asthma
Bibliographic record
Abstract
Semaphorin3E (Sema3E) is a protein that plays a critical role in immunity to diseases, including asthma, by regulating cell migration, proliferation, and angiogenesis. Little is known about the role of Sema3E in immunoglobulin E (IgE) regulation. Recent data showed that Sema3e-/- mice have a significantly higher serum level of total and allergen-specific IgE in allergic asthma. These results strongly indicate a crucial involvement of Sema3E in modulating IgE production. In my project, we hypothesised that Sema3E negatively regulates IgE levels through germinal center (GC) responses. To investigate the regulatory role of Sema3E in IgE production and GC formation, Sema3e-/- and WT mice underwent an acute HDM challenge. Flow cytometry was performed to investigate the number of GC B cells, T follicular helper (Tfh) cells, and inflammatory cells. The antibodies and inflammatory cytokines levels were detected by ELISA and Mesoscale, respectively. Immunofluorescence (IF) staining and H&E staining were performed to investigate GC formation and lung inflammation, respectively. Additionally, to check if Sema3E plays a role through the ICOS/ICOS-L pathway, GC formation was blocked by intraperitoneal administration of anti-ICOS-L or rat IgG as an isotype control. The results demonstrated that at the steady-state, Sema3e-/- mice had a significantly higher baseline number of GC B cells, Tfh cells, plasmablasts, plasma cells, and serum IgE and IgG1 than the WT counterparts. Interestingly, baseline expression of IgE and IgG by B cells is regulated by Sema3E, and Sema3e-/- mice demonstrated higher expression of IgE and IgG1 in their B cells. Upon immunization with HDM, Sema3e-/- mice exhibited enhanced GC responses, IgE production, and lung inflammation. We demonstrated that the deletion of Sema3E in mice led to an increase in the expression of ICOS on CD4+ T cells and disruption of ICOS/ICOS-L signalling, remarkably reducing the number of inflammatory cells, plasma cells, serum levels of IgE and IgG1, and lung inflammation indicating the importance of ICOS/ICOS-L signalling pathway in Sema3E regulatory effect. In conclusion, Sema3E plays a critical regulatory role in GC response and IgE production at the steady-state and post-immunization through ICOS/ICOS-L signalling, suggesting the critical negative regulatory role of Sema 3E in allergic inflammation.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| 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".