Nasal expression of bitter taste receptors TAS2R in asthma: associations with the disease control, inflammation and bronchial obstruction

Introduction. Bitter taste receptors (TAS2Rs) can be expressed in airway epithelium and are of interest as therapeutic targets for asthma treatment. In a pilot study, we previously identified the most highly expressed TAS2Rs in the nasal epithelium of asthma patients and healthy individuals using NGS. Aim. To determine the relationship between TAS2Rs expression in the nasal epithelium and the disease control, inflammatory markers, airway patency and remodeling in patients with asthma. Materials and methods. The study included 173 patients with asthma (mean age: 46.0 ± 1.13 years; 60% females) of varying severity (56.4% – mild, 41.3% – moderate, 2.3% – severe asthma), predominantly with an uncontrolled disease course (71%). The patients underwent spirometric examination with obstruction reversibility testing and computed tomography (CT) based morphometric analysis of B1 and B10 segmental bronchi following bronchodilator administration. Serum concentrations of total IgE and cytokines (IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IFN-γ, TNF-α, IL-17A, IL-17F, and IL-22) were measured by ELISA and microparticle-based immunofluorescence assay (LEGENDplex), respectively. Expression of TAS2R4, TAS2R5, TAS2R14, TAS2R20, TAS2R31 and TAS2R38 genes was determined at mRNA level by quantitative reverse transcription PCR (qRT-PCR) in samples obtained from inferior turbinate brush biopsies. Results. Expression of all genes except TAS2R4 showed significant correlations. Decreased asthma control, as assessed by the ACT questionnaire, was associated with increased expression of TAS2R20 (β = -0.20, p = 0.03) and TAS2R38 (β = -0.20, p = 0.02) after adjustment for gender, age, body mass index, smoking index, FEV₁, and IgE level using multiple linear regression. No correlations were found between TAS2R gene expression and lung function parameters or bronchodilator response. Using PLS-SEM analysis, it was found that Th17-driven inflammation, primarily determined by IL-17A levels, is the main factor associated with both CT signs of bronchial remodeling (an inverse association with bronchial size (β = -0.57, p < 0.001) and a direct association with bronchial wall thickening (β = 0.34, p = 0.05)) as well as with increased TAS2R expression (most significantly with TAS2R5 (β = 0.40, p = 0.01) and TAS2R20 (β = 0.41, p = 0.01)). Bronchial remodeling itself was also associated with upregulation of TAS2Rs, particularly TAS2R5 (R² = 0.17, p = 0.002) and TAS2R20 (R² = 0.15, p = 0.006). However, a significant association with expression level was observed only for the latent variable reflecting bronchial size (β = -0.33, p < 0.001 for both TAS2R5 and TAS2R20). Conclusion. We found evidence of increased TAS2R genes expression with worsening asthma control, as well as in patients with more pronounced bronchial remodeling and elevated serum IL-17A. Given that TAS2R upregulation appears to be a secondary, compensatory response, TAS2R5 and TAS2R20 receptors emerge as the most promising targets for further investigation. 

1. Yuan L., Tao J., Wang J., She W., Zou Y., Li R., Ma Y., Sun C., Bi S., Wei S., Chen H., Guo X., Tian H., Xu J., Dong Y., Ma Y., Sun H., Lv W., Shang Z., Jiang Y., Lv H., Zhang M. Global, regional, national burden of asthma from 1990 to 2021, with projections of incidence to 2050: a systematic analysis of the global burden of disease study 2021. EClinical- Medicine 2025; 80:103051. https://doi.org/10.1016/j.eclinm.2024.103051

2. Zhang W., Zhang Y., Li L., Chen R., Shi F. Unraveling heterogeneity and treatment of asthma through integrating multi-omics data. Front. Allergy 2024; 5:1496392. https://doi.org/10.3389/falgy.2024.1496392

3. Sharma P., Yi R., Nayak A.P., Wang N., Tang F., Knight M.J., Pan S., Oliver B., Deshpande D.A. Bitter taste receptor agonists mitigate features of allergic asthma in mice. Sci. Rep. 2017; 7:46166. https://doi.org/10.1038/srep46166

4. Naumov D.E., Gassan D.A., Kotova O.O., Sheludko E.G., Afanas’eva E.Yu., Konev А.V., Perelman J.M. [Analysis of TAS2R bitter taste receptors expression in the nasal epithelium of asthma patients by next generation sequencing]. Bûlleten' fiziologii i patologii dyhaniâ = Bulletin Physiology and Pathology of Respiration 2025; 95:8–17 (in Russian). https://doi.org/10.36604/1998-5029-2025-95-8-17

5. Zeng G., Zhang G., Chen X. Th1 cytokines, true functional signatures for protective immunity against TB? Cell. Mol. Immunol. 2018; 15(3):206–215. https://doi.org/10.1038/cmi.2017.113

6. Webster H.C., Gamino V., Andrusaite A.T., Ridgewell O.J., McCowan J., Shergold A.L., Heieis G.A., Milling S.W.F., Maizels R.M., Perona-Wright G. Tissue-based IL-10 signaling in helminth infection limits IFNγ expression and promotes the intestinal Th2 response. Mucosal Immunol. 2022; 15(6):1257–1269. https://doi.org/10.1038/s41385-022-00513-y

7. Roostaee A., Yaghobi R., Afshari A., Jafarinia M. Regulatory role of T helper 9/interleukin-9: transplantation view. Heliyon 2024; 10(4):e26359. https://doi.org/10.1016/j.heliyon.2024.e26359

8. Guglani L., Khader S.A. Th17 cytokines in mucosal immunity and inflammation. Curr. Opin. HIV AIDS 2010; 5(2):120–127. https://doi.org/10.1097/COH.0b013e328335c2f6

9. Zhang K., Chen L., Zhu C., Zhang M., Liang C. Current knowledge of Th22 cell and IL-22 functions in infectious diseases. Pathogens 2023; 12(2):176. https://doi.org/10.3390/pathogens12020176

10. Fokkens W., Reitsma S. Unified airway disease: a contemporary review and introduction. Otolaryngol. Clin. North. Am. 2023; 56(1):1–10. https://doi.org/10.1016/j.otc.2022.09.001

11. Camoretti-Mercado B., Lockey R.F. Bitter taste receptors in the treatment of asthma: opportunities and challenges. J. Allergy Clin. Immunol. 2020; 146(4):776–779. https://doi.org/10.1016/j.jaci.2020.04.036

12. Ziegler F., Steuer A., Di Pizio A., Behrens M. Physiological activation of human and mouse bitter taste receptors by bile acids. Commun. Biol. 2023; 6(1):612. https://doi.org/10.1038/s42003-023-04971-3

13. Nakada E.M., Bhakta N.R., Korwin-Mihavics B.R., Kumar A., Chamberlain N., Bruno S.R., Chapman D.G., Hoffman S.M., Daphtary N., Aliyeva M., Irvin C.G., Dixon A.E., Woodruff P.G., Amin S., Poynter M.E., Desai D.H., Anathy V. Conjugated bile acids attenuate allergen-induced airway inflammation and hyperresponsiveness by inhibiting UPR transducers. JCI Insight. 2019; 4(9):e98101. https://doi.org/10.1172/jci.insight.98101

14. Kook J.H., Kim H.K., Kim H.J., Kim K.W., Kim T.H., Kang K.R., Oh D.J., Lee S.H. Increased expression of bitter taste receptors in human allergic nasal mucosa and their contribution to the shrinkage of human nasal mucosa. Clin. Exp. Allergy 2016; 46(4):584-601. https://doi.org/10.1111/cea.12727

15. Song M., Liang J., Wang L., Li W., Jiang S., Xu S., Tang L., Du Q., Liu G., Meng H., Zhai D., Shi S., Yang Y., Zhang L., Zhang B. IL-17A functions and the therapeutic use of IL-17A and IL-17RA targeted antibodies for cancer treatment. Int. Immunopharmacol. 2023; 123:110757. https://doi.org/10.1016/j.intimp.2023.110757

16. Mills K.H.G. IL-17 and IL-17-producing cells in protection versus pathology. Nat. Rev. Immunol. 2023; 23(1):38– 54. https://doi.org/10.1038/s41577-022-00746-9

17. Freund J.R., Lee R.J. Taste receptors in the upper airway. World J. Otorhinolaryngol. Head Neck Surg. 2018; 4(1):67–76. https://doi.org/10.1016/j.wjorl.2018.02.004

18. Rahmawati S.F., Te Velde M., Kerstjens H.A.M., Dömling A.S.S., Groves M.R., Gosens R. Pharmacological rationale for targeting IL-17 in asthma. Front. Allergy 2021; 2:694514. https://doi.org/10.3389/falgy.2021.694514

19. Zhou Y., Toh M.L., Zrioual S., Miossec P. IL-17A versus IL-17F induced intracellular signal transduction pathways and modulation by IL-17RA and IL-17RC RNA interference in AGS gastric adenocarcinoma cells. Cytokine 2007; 38(3):157–164. https://doi.org/10.1016/j.cyto.2007.06.002

20. Goedken E.R., Su Z., Lipovsky A., Kannan A., Chu K.L., Ciura S., Foley S.E., Frank K.E., Goess C.A., Gopalakrishnan S., Greszler S.N., Khan H.A., Leys L.J., King J.J., Mathieu S.L., Panchal S.C., Paulsboe S., Perham M., Ramos A.L., Slivka P.F., Srikumaran M., Webster M.P., Wambeke E.L., Zhu H., Scott V.E., McGaraughty S., Honore P. Small molecule interleukin (IL) 17A/A antagonists and antibodies blocking both IL17A/A and IL17A/F demonstrate equivalent degrees of efficacy in preclinical models of skin and joint inflammation. J. Pharmacol. Exp. Ther. 2025; 392(4):103525. https://doi.org/10.1016/j.jpet.2025.103525

21. Grassin-Delyle S., Salvator H., Mantov N., Abrial C., Brollo M., Faisy C., Naline E., Couderc L.J., Devillier P. Bitter taste receptors (TAS2Rs) in human lung macrophages: receptor expression and inhibitory effects of TAS2R agonists. Front. Physiol. 2019; 10:1267. https://doi.org/10.3389/fphys.2019.01267