Bitter Taste Receptors: an Answer to Comprehensive Asthma Control?
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Purpose of Review
Asthma is marked by peculiar pathological features involving airway contraction, an impinging inflammation in the lungs, and an inexorably progressive remodeling of pulmonary architecture. Current medications for management of asthma exacerbations fail to optimally mitigate these pathologies, which is partly due to the intrinsic heterogeneity in the development and progression of asthma within different populations. In recent years, the discovery of the ectopic expression of TAS2Rs in extraoral tissues and different cell types, combined with significant strides in gaining mechanistic understanding into receptor signaling and function, has revealed the potential to target TAS2Rs for asthma relief.
TAS2R activation leads to relaxation of airway smooth muscle cells and bronchodilation. In addition, findings from preclinical studies in murine model of asthma suggest that TAS2R agonists inhibit allergen-induced airway inflammation, remodeling, and hyperresponsiveness.
In this review, we expand on the opportunity presented by TAS2Rs in the development of a comprehensive asthma treatment that overcomes the limitations set forth by current asthma therapeutics.
KeywordsAsthma TAS2R Bitter tastant Airway smooth muscle SCC
This study was supported by grants from American Asthma Foundation, and National Heart, Lung, Blood Institute Grant R01HL137030.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: •• Of major importance
- 8.•• Luo XC, Chen ZH, Xue JB, Zhao DX, Lu C, Li YH, et al. Infection by the parasitic helminth Trichinella spiralis activates a Tas2r-mediated signaling pathway in intestinal tuft cells. Proc Natl Acad Sci U S A. 2019;116(12):5564–9. Study demostrated the role of TAS2Rs in orchestrating parasite-induced Th2 immune response. CrossRefPubMedPubMedCentralGoogle Scholar
- 17.•• Deshpande DA, Wang WC, McIlmoyle EL, Robinett KS, Schillinger RM, An SS, et al. Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction. Nat Med. 2010;16(11):1299–304. Study for the first time demostrated the expression and functional effect of TAS2Rs on human ASM cells. CrossRefPubMedPubMedCentralGoogle Scholar
- 20.•• Sharma P, Yi R, Nayak AP, Wang N, Tang F, Knight MJ, et al. Bitter taste receptor agonists mitigate features of allergic asthma in mice. Sci Rep. 2017;7:46166. This study demonstrated the in vivo effectiveness of TAS2R agonists on features of asthma in multiple murine models. CrossRefPubMedPubMedCentralGoogle Scholar
- 47.Prakash YS, Halayko AJ, Gosens R, Panettieri RA Jr, Camoretti-Mercado B, Penn RB, et al. An Official American Thoracic Society Research statement: current challenges facing research and therapeutic advances in airway remodeling. Am J Respir Crit Care Med. 2017;195(2):e4–e19.CrossRefPubMedGoogle Scholar
- 59.•• Orsmark-Pietras C, James A, Konradsen JR, Nordlund B, Soderhall C, Pulkkinen V, et al. Transcriptome analysis reveals upregulation of bitter taste receptors in severe asthmatics. Eur Respir J. 2013;42(1):65–78. This is a clinical study demonstrating the expression changes in peripheral blood leukocytes TAS2Rs in asthmatics. CrossRefPubMedGoogle Scholar
- 66.•• Ekoff M, Choi JH, James A, Dahlen B, Nilsson G, Dahlen SE. Bitter taste receptor (TAS2R) agonists inhibit IgE-dependent mast cell activation. J Allergy Clin Immunol. 2014;134(2):475–8. This study demonstrated the functional effect of TAS2R activation in mast cells obtained from human subjects. CrossRefPubMedGoogle Scholar
- 67.Maurer S, Wabnitz GH, Kahle NA, Stegmaier S, Prior B, Giese T, et al. Tasting Pseudomonas aeruginosa biofilms: human neutrophils express the bitter receptor T2R38 as sensor for the quorum sensing molecule N-(3-oxododecanoyl)-l-homoserine lactone. Front Immunol. 2015;6:369.CrossRefPubMedPubMedCentralGoogle Scholar