Bitter Taste Receptor T2r38 in URI and Chronic Rhinosinusitis
Bitter Taste Receptor T2r38 in URI and Chronic Rhinosinusitis
T2R38 is part of an interkingdom eavesdropping system by which mammalian cells intercept bacterial quorum-sensing communications. A summary of current evidence linking T2R38s with sinonasal innate immunity is shown in Table 1. Further prospective clinical studies on TAS2R38 genotype and CRS susceptibility, including the influence of TAS2R38 genotype on patient outcomes, are currently ongoing. However, the T2R38 pathway is already a potential therapeutic target to promote endogenous immune responses in patients with upper respiratory infections. One caveat, though, is that there would likely be a large subset of patients who would be suboptimally responsive to the treatment with T2R38 agonists (i.e. PAV/AVI and AVI/AVI individuals). It is, thus, still necessary to further define T2R38 signaling mechanisms in airway cells, as well as to identify other T2Rs that activate similar responses.
It is also likely that other T2R isoforms expressed in other airway cell types may have important clinical relevance. Table 2 shows a representative list of known T2R expression in the airway. In particular, the genetics of T2Rs in nasal solitary chemosensory cells may play an important role in CRS susceptibility. Solitary chemosensory cells control antimicrobial peptide secretion in humans and both breath-holding and inflammation in mice. Clinical consequences remain to be determined.
A better understanding of the T2R isoforms expressed in ciliated cells will speed identification of potential compounds that stimulate innate defenses. The role of T2Rs as global mediators of innate immunity was recently supported by a report demonstrating that T2R-expressing chemosensory cells in the rodent urethra respond to the bitter compounds, as well as heat-inactivated uropathogenic Escherichia coli; activation of these cells causes release of ACh to activate the bladder detrusor muscle. Further investigation of T2Rs in innate immunity will likely result in a significant clinical impact on the airway and other organ systems.
Conclusion
T2R38 is part of an interkingdom eavesdropping system by which mammalian cells intercept bacterial quorum-sensing communications. A summary of current evidence linking T2R38s with sinonasal innate immunity is shown in Table 1. Further prospective clinical studies on TAS2R38 genotype and CRS susceptibility, including the influence of TAS2R38 genotype on patient outcomes, are currently ongoing. However, the T2R38 pathway is already a potential therapeutic target to promote endogenous immune responses in patients with upper respiratory infections. One caveat, though, is that there would likely be a large subset of patients who would be suboptimally responsive to the treatment with T2R38 agonists (i.e. PAV/AVI and AVI/AVI individuals). It is, thus, still necessary to further define T2R38 signaling mechanisms in airway cells, as well as to identify other T2Rs that activate similar responses.
It is also likely that other T2R isoforms expressed in other airway cell types may have important clinical relevance. Table 2 shows a representative list of known T2R expression in the airway. In particular, the genetics of T2Rs in nasal solitary chemosensory cells may play an important role in CRS susceptibility. Solitary chemosensory cells control antimicrobial peptide secretion in humans and both breath-holding and inflammation in mice. Clinical consequences remain to be determined.
A better understanding of the T2R isoforms expressed in ciliated cells will speed identification of potential compounds that stimulate innate defenses. The role of T2Rs as global mediators of innate immunity was recently supported by a report demonstrating that T2R-expressing chemosensory cells in the rodent urethra respond to the bitter compounds, as well as heat-inactivated uropathogenic Escherichia coli; activation of these cells causes release of ACh to activate the bladder detrusor muscle. Further investigation of T2Rs in innate immunity will likely result in a significant clinical impact on the airway and other organ systems.
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