Lineage specific role of Ship1 in development of allergic airway inflammation
Bibliographic record
Abstract
The PI3K pathway is a potent mediator of several functions associated with asthma pathogenesis, including supporting leukocyte survival, activation, migration and cytokine release. Proper negative regulation of this pathway is integral in order to restrict overactive immune responses. Negative regulation of PI3K is predominantly controlled by the lipid phosphatases PTEN and SHIP-1. Inpp5d ( Ship1 ) deficient mice develop spontaneous airway inflammation and have enhanced sensitivity to allergen induced airway inflammation. We hypothesized that deleting Ship1 expression specifically in lineages known to be crucial for adaptive Th2 responses would uncover more subtle effects that could either positively or negatively regulate disease severity in a mouse model of allergic airway inflammation (AAI). Ship1 expression was deleted in B cell, T cell and dendritic cell (DC) lineages and the resulting Ship1 , Ship1 and Ship1 mice were exposed to house dust mite (HDM) antigen over an 18-day period. Infiltrating leukocytes in the bronchoalveolar lavage (BAL) and lung, serum antibody levels and Th1 and Th2 cytokine responses were quantified to assess disease severity. Deletion of Ship1 in either the B cell, T cell or DC lineages did not result in spontaneous airway inflammation, and loss of Ship1 in the B cell linage did not affect HDM-induced AAI. Surprisingly, loss of Ship1 in either of the T cell or DC lineages protected from development of AAI by skewing the HDM-induced immune response to a Th1 phenotype instead of the characteristic Th2 phenotype associated with allergic asthma. While loss of Ship1 expression throughout the hematopoietic populations leads to spontaneous lung inflammation, selective deletion of Ship1 in T cells and DCs impairs the formation of an adaptive Th2 response and protects from the development of AAI.
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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 | 0.000 |
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 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".