Loss of LMAN1 in airway epithelial cells improves mitochondrial function in response to Alternaria alternata 4048
Bibliographic record
Abstract
Abstract Description Severe asthma is characterized by asthma that is inadequately controlled despite adherence to high-dose treatment. Alternaria alternata (A alt) has been linked to both asthma severity and asthma exacerbations. We have identified LMAN1 as a receptor which binds A alt in vitro. Using an in vivo model of severe asthma, loss of LMAN1 was shown to influence airway hyperresponsiveness, ILC2 cells, alveolar macrophages and neutrophils in a sex-specific manner. However, the molecular mechanisms responsible for such effects are still unclear. To this end, we have used CRISPR/Cas9 to delete LMAN1 in (male) BEAS-2B cells and perform transcriptomic analysis for the response to A alt. Differential gene expression and pathway analysis pointed to the involvement of LMAN1 in mitochondrial function, immune responses and apoptosis. To further investigate these processes, we assessed cytokine production, mitochondrial respiration, mitochondrial ROS production, Ca2+ signaling and signal transduction pathways in LMAN1 sufficient and LMAN1 deficient BEAS-2B cells in response to A alt. Our data thus far indicates that unlike control cells, cells lacking LMAN1 produced less ROS and were better able to deal with mitochondrial stress in response to A alt exposure. Loss of LMAN1 also inhibited A alt-induced activation of caspases 3, 7 and 8, and phosphorylation of p38, and JNK MAPKs. Overall, these data suggest a potential beneficial effect for therapies targeting LMAN1 within the airway epithelium. Funding Sources This work was supported through NIH R01HL162897 awarded to J.T.T-A. Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)
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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".