The Role of Bitter Taste Receptors (T2Rs) in Cystic Fibrosis
Bibliographic record
Abstract
Introduction Bitter taste receptors (T2Rs) belong to the G protein‐coupled receptor superfamily. In humans, 25 T2Rs perform a chemosensory function, however very little is known regarding their expression and function in extraoral tissues. Recent studies showed that T2Rs recognize quorum‐sensing molecules (QSMs) secreted by bacteria. Cystic fibrosis (CF) is a genetic disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). The opportunistic pathogen Pseudomonas aeruginosa colonizes CF airways and secretes QSMs, which increase intracellular calcium and modulate innate immune responses through unidentified cell surface receptors. We hypothesized that T2Rs are expressed in epithelial cells of human airways, where they mediate QSM responses and modulate immune responses in CF. Methods and Results We monitored the expression of T2Rs in primary CF and non‐CF bronchial epithelial cells. Cells were studied at both the mRNA and protein levels using qPCR and FACS analysis, respectively. We found similar expression of T2Rs in non‐CF and CF cells. Next we treated these cells with a number of QSMs and measured the intracellular calcium mobilized. We found that the calcium mobilized was sensitive to the PLC inhibitor U‐73122 suggesting that the signaling in these cells occurs predominantly through the QSM‐T2R‐Gαβγ‐PLC pathway. To further characterize the candidate T2Rs that may recognize specific QSMs and modulate signaling in CF, a heterologous expression system was used to stably express selected T2Rs and study the effects of QSMs. We found that a single QSM (for example, 3‐oxo‐C12‐AHL) can activate more than one T2R, and that multiple QSMs can activate the same T2R. Conclusions T2Rs are expressed in bronchial epithelial cells and are functional. Although expression was not altered in CF cells, these results suggest there is a synergistic effect of QSMs on T2R signaling in CF airways and provides a rationale for further research on the pathophysiological function of T2Rs in extraoral tissues. These mechanistic studies should improve our understanding of host response mechanisms and may lead to new therapeutic approaches for CF that target T2Rs. Support or Funding Information Natural Sciences and Engineering Research Council of Canada (NSERC)
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| 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".