Anti-alarmin approaches entering clinical trials
Bibliographic record
Abstract
PURPOSE OF REVIEW: The alarmins, thymic stromal lymphopoietin (TSLP), interleukin (IL)-25 and IL-33, are upstream regulators of T2 (type 2) inflammation and found to be expressed at high levels in airway epithelium of patients with T2 asthma. This review will summarize how alarmins regulate the inflamed asthmatic airways through previously described and newly identified mechanisms. RECENT FINDINGS: Alarmins drive allergic and nonallergic asthma through activation of innate lymphoid cell 2 (ILC2), which are a rich source of cytokines such as IL-5 and IL-13, with resulting effects on eosinophilopoeisis and remodelling, respectively. Findings from bronchial allergen challenges have illustrated widespread expression of alarmins and their receptors across many effector cells in airways, and recent studies have emphasized alarmin regulation of CD4 T lymphocytes, eosinophils and basophils, and their progenitors. Furthermore, a link between alarmins and lipid mediators is being uncovered. SUMMARY: Alarmins can drive well defined inflammatory pathways through activation of dendritic cells and polarizing T cells to produce type 2 cytokines, as well as they can directly activate many other effector cells that play a central role in allergic and nonallergic asthma. Clinical trials support a central role for TSLP in driving airway inflammation and asthma exacerbations, while ongoing trials blocking IL-33 and IL-25 will help to define their respective role in asthma.
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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 | 0.008 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.007 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 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 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".