An Investigation into the Expression and Role of TSLP During the Anti-Viral Response of Airway Epithelial Cells
Bibliographic record
Abstract
The airway epithelium is one of the first lines of defence against airborne pathogens. Airway epithelial cells are crucial in initiating and directing the subsequent immune response to deal with invading pathogens rapidly. An early mediator produced by epithelial cells is the alarmin cytokine, thymic stromal lymphopoietin (TSLP), which is known to activate several immune cells. However, overexpression of TSLP is the underlying cause of several diseases, including asthma and allergy, and contributes to increased pathophysiology of other respiratory viruses. Little is known regarding the role of the airway epithelium and TSLP during SARS- CoV-2 infections, the virus responsible for COVID-19. Additionally, the role of TSLP autocrine/paracrine signalling within the epithelium is poorly understood. We investigated the expression of TSLP in COVID-19 patients at the University of Alberta hospital and found that they had a trend towards elevated systemic TSLP, although this was not statistically significant, which correlated with increased hospitalization duration. Several other cytokines were measured, and significant plasma IL-15 and CXCL10/IP-10 increases were detected. In cultured bronchial epithelial cells from healthy donors, we measured significant increases in intracellular and supernatant TSLP expression in response to SARS-CoV-2 infection but not in nasal or gut epithelial cells. To increase our understanding of the role TSLP has within the epithelium, we created a simple model to virally induce epithelial-derived TSLP production and block it using TSLP- neutralizing antibodies. We confirmed that the viral mimetic poly I:C can induce a strong TSLP response through a TLR3-specific mechanism. Furthermore, we characterized the expression of several key antiviral and inflammatory genes, including TSLP, TSLPR, RIG-I, MDA5, IL-25, IL-33, TL1A) and interferons. For the first time, we observed that TL1A is significantly I upregulated in airway epithelial cells in response to poly I:C treatment. Additionally, we made a novel observation showing that epithelial-derived TSLP may contribute to regulating antiviral receptors such as RIG-I and MDA5. Our goal is that the data presented in this thesis sheds light on the vital role of the airway epithelium and TSLP during COVID-19 infections and the broader context of antiviral defences. Our findings are intended to increase our understanding and appreciation for the important role of epithelial cells during viral infections.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".