{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T03:52:06Z","timestamp":1794369126549,"version":"4.9.0"},"reference-count":53,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T00:00:00Z","timestamp":1664928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Emalie Gutterman Memorial Endowed Fund (USA)","award":["343\/22"],"award-info":[{"award-number":["343\/22"]}]},{"name":"Israel Science Foundation","award":["343\/22"],"award-info":[{"award-number":["343\/22"]}]},{"name":"Aimwell Charitable Trust (UK)","award":["343\/22"],"award-info":[{"award-number":["343\/22"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>Allergic rhinitis (AR) is a common rhinopathy that affects up to 30% of the adult population. It is defined as an inflammation of the nasal mucosa, develops in allergic individuals, and is detected mostly by a positive skin-prick test. AR is characterized by a triad of nasal congestion, rhinorrhea, and sneezing. Mast cells (MCs) are innate immune system effector cells that play a pivotal role in innate immunity and modulating adaptive immunity, rendering them as key cells of allergic inflammation and thus of allergic diseases. MCs are typically located in body surfaces exposed to the external environment such as the nasal mucosa. Due to their location in the nasal mucosa, they are in the first line of defense against inhaled substances such as allergens. IgE-dependent activation of MCs in the nasal mucosa following exposure to allergens in a sensitized individual is a cardinal mechanism in the pathophysiology of AR. This review is a comprehensive summary of MCs\u2019 involvement in the development of AR symptoms and how classical AR medications, as well as emerging AR therapies, modulate MCs and MC-derived mediators involved in the development of AR.<\/jats:p>","DOI":"10.3390\/biomedicines10102486","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T00:07:43Z","timestamp":1665187663000},"page":"2486","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Allergic Rhinitis: Pathophysiology and Treatment Focusing on Mast Cells"],"prefix":"10.3390","volume":"10","author":[{"given":"Yara","family":"Zoabi","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, School of Pharmacy, Faculty of Medicine, Hebrew University, Jerusalem 9112002, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Levi-Schaffer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, School of Pharmacy, Faculty of Medicine, Hebrew University, Jerusalem 9112002, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron","family":"Eliashar","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\/HNS, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13601-019-0303-6","article-title":"Benefits and harm of systemic steroids for short- and long-term use in rhinitis and rhinosinusitis: An EAACI position paper","volume":"10","author":"Hox","year":"2020","journal-title":"Clin. Transl. Allergy"},{"key":"ref_2","unstructured":"Justiz Vaillant, A.A., Vashisht, R., and Zito, P.M. (2022, September 24). Immediate Hypersensitivity Reactions, StatPearls, Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK513315\/."},{"key":"ref_3","first-page":"108","article-title":"International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis: ICAR: Allergic Rhinitis","volume":"8","author":"Wise","year":"2018","journal-title":"Int. Forum. Allergy Rhinol."},{"key":"ref_4","unstructured":"Akhouri, S., and House, S.A. (2021, November 07). Allergic Rhinitis, StatPearls, Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK538186\/."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/S0091-6749(97)70281-1","article-title":"Allergic rhinitis to grass pollen: Measurement of inflammatory mediators of mast cell and eosinophils in native nasal fluid lavage and in serum out of and during pollen season","volume":"100","author":"Mansueto","year":"1997","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s13223-018-0280-7","article-title":"Allergic rhinitis","volume":"14","author":"Small","year":"2018","journal-title":"Allergy Asthma Clin. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"747364","DOI":"10.3389\/fphar.2021.747364","article-title":"Latest Progresses in Allergic Diseases Biomarkers: Asthma and Atopic Dermatitis","volume":"12","author":"Puzzovio","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Walsh, G.M. (2021). Update on Eosinophil Interaction with Mast Cells: The Allergic Effector Unit. Eosinophils, Springer.","DOI":"10.1007\/978-1-0716-1095-4"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e042380","DOI":"10.1136\/bmjopen-2020-042380","article-title":"Prevalence of atopic dermatitis, asthma and rhinitis from infancy through adulthood in rural Bangladesh: A population-based, cross-sectional survey","volume":"10","author":"Pedersen","year":"2020","journal-title":"BMJ Open"},{"key":"ref_10","first-page":"1","article-title":"European Position Paper on Rhinosinusitis and Nasal Polyps 2020","volume":"58","author":"Fokkens","year":"2020","journal-title":"Rhinol. Off. Organ Int. Rhinol. Soc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1159\/000518924","article-title":"The Underestimated Role of Mast Cells in the Pathogenesis of Rhinopathies","volume":"183","author":"Gelardi","year":"2022","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.iac.2019.12.010","article-title":"The Role of Allergic Rhinitis in Chronic Rhinosinusitis","volume":"40","author":"Helman","year":"2020","journal-title":"Immunol. Allergy Clin. North Am."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"463","DOI":"10.2147\/JAA.S237463","article-title":"The Role of Mast Cells in Aspirin-Exacerbated Respiratory Disease (AERD) Pathogenesis: Implications for Future Therapeutics","volume":"13","author":"Kuruvilla","year":"2020","journal-title":"J. Asthma Allergy"},{"key":"ref_14","first-page":"620","article-title":"Mast Cell: A Multi-Functional Master Cell","volume":"6","author":"Dileepan","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"50","DOI":"10.3389\/fimmu.2020.00050","article-title":"SG-SP1 Suppresses Mast Cell-Mediated Allergic Inflammation via Inhibition of Fc\u03b5RI Signaling","volume":"11","author":"Kim","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Katsoulis-Dimitriou, K., Kotrba, J., Voss, M., Dudeck, J., and Dudeck, A. (2020). Mast Cell Functions Linking Innate Sensing to Adaptive Immunity. Cells, 9.","DOI":"10.20944\/preprints202011.0016.v1"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s40413-016-0094-3","article-title":"Biomarkers of the involvement of mast cells, basophils and eosinophils in asthma and allergic diseases","volume":"9","author":"Metcalfe","year":"2016","journal-title":"World Allergy Organ. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"294","DOI":"10.3389\/fphar.2019.00294","article-title":"Modulation of Allergic Inflammation in the Nasal Mucosa of Allergic Rhinitis Sufferers With Topical Pharmaceutical Agents","volume":"10","author":"Watts","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1159\/000515918","article-title":"CD48 Expression on Eosinophils in Nasal Polyps of Chronic Rhinosinusitis Patients","volume":"182","author":"Zoabi","year":"2021","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3176","DOI":"10.3389\/fimmu.2018.03176","article-title":"Human Dendritic Cells: Their Heterogeneity and Clinical Application Potential in Cancer Immunotherapy","volume":"9","author":"Patente","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1016\/j.jaci.2018.11.029","article-title":"Mast cell granules: Modulating adaptive immune response remotely","volume":"143","author":"Jain","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.12688\/f1000research.15367.1","article-title":"Recent advances in allergic rhinitis","volume":"7","author":"Hoyte","year":"2018","journal-title":"F1000Research"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"214","DOI":"10.3389\/fphys.2016.00214","article-title":"The Therapeutic Potential of Targeting Cytokine Alarmins to Treat Allergic Airway Inflammation","volume":"7","author":"Sy","year":"2016","journal-title":"Front. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Whetstone, C.E., Ranjbar, M., Omer, H., Cusack, R.P., and Gauvreau, G.M. (2022). The Role of Airway Epithelial Cell Alarmins in Asthma. Cells, 11.","DOI":"10.3390\/cells11071105"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3845","DOI":"10.1016\/j.jaip.2021.07.008","article-title":"The allergic effector unit: From basic science to drug-targetable mast cell\u2013eosinophil interactions in patients","volume":"9","author":"Puzzovio","year":"2021","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3389\/fmed.2018.00049","article-title":"Targeting the Interleukin-5 Pathway for Treatment of Eosinophilic Conditions Other than Asthma","volume":"5","author":"Roufosse","year":"2018","journal-title":"Front. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1016\/j.jaci.2022.01.019","article-title":"Tezepelumab administration in moderate-to-severe uncontrolled asthma: Is it all about eosinophils?","volume":"149","author":"Puzzovio","year":"2022","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Iwasaki, N., Terawaki, S., Shimizu, K., Oikawa, D., Sakamoto, H., Sunami, K., and Tokunaga, F. (2021). Th2 cells and macrophages cooperatively induce allergic inflammation through histamine signaling. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0248158"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"537","DOI":"10.5114\/aoms.2017.68534","article-title":"New antihistamines\u2014Perspectives in the treatment of some allergic and inflammatory disorders","volume":"15","author":"Tatarkiewicz","year":"2019","journal-title":"Arch. Med. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.3389\/fimmu.2018.01873","article-title":"The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation: The Hunt for New Therapeutic Targets","volume":"9","author":"Thangam","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1002\/alr.21625","article-title":"Expression of leukotriene and its receptors in eosinophilic chronic rhinosinusitis with nasal polyps: Expression of LT and its receptors in ECRS","volume":"6","author":"Wu","year":"2016","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_32","unstructured":"Cuzzo, B., and Lappin, S.L. (2022, September 24). Physiology, Leukotrienes, StatPearls, Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK526114\/."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Lee, K., Lee, S.H., and Kim, T.H. (2020). The Biology of Prostaglandins and Their Role as a Target for Allergic Airway Disease Therapy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051851"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1159\/000510166","article-title":"Elevated Serum Level of CD48 in Patients with Intermittent Allergic Rhinitis","volume":"182","author":"Branicka","year":"2021","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1002\/iid3.545","article-title":"Adult allergic rhinitis sufferers have unique nasal mucosal and peripheral blood immune gene expression profiles: A case\u2013control study","volume":"10","author":"Watts","year":"2022","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13223-020-00436-y","article-title":"Towards definitive management of allergic rhinitis: Best use of new and established therapies","volume":"16","author":"Hossenbaccus","year":"2020","journal-title":"Allergy Asthma Clin. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1080\/13543784.2019.1571581","article-title":"New drugs in early-stage clinical trials for allergic rhinitis","volume":"28","author":"Heffler","year":"2019","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"148","DOI":"10.4168\/aair.2011.3.3.148","article-title":"Management of Rhinitis: Allergic and Non-Allergic","volume":"3","author":"Tran","year":"2011","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41533-016-0001-y","article-title":"An algorithm recommendation for the pharmacological management of allergic rhinitis in the UK: A consensus statement from an expert panel","volume":"27","author":"Lipworth","year":"2017","journal-title":"NPJ Prim. Care Respir. Med."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Jo-Watanabe, A., Okuno, T., and Yokomizo, T. (2019). The Role of Leukotrienes as Potential Therapeutic Targets in Allergic Disorders. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20143580"},{"key":"ref_41","unstructured":"Page, C.P., and Barnes, P.J. (2016). Leukotriene Receptor Antagonists and Antiallergy Drugs. Pharmacology and Therapeutics of Asthma and COPD, Springer International Publishing."},{"key":"ref_42","unstructured":"Minutello, K., and Gupta, V. (2022, September 24). Cromolyn Sodium, StatPearls, Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK557473\/."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"106172","DOI":"10.1016\/j.phrs.2022.106172","article-title":"Cromolyn Sodium differentially regulates human mast cell and mouse leukocyte responses to control allergic inflammation","volume":"178","author":"Puzzovio","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_44","first-page":"501","article-title":"Omalizumab for the treatment of allergic rhinitis: A systematic review and meta-analysis","volume":"59","author":"Tsabouri","year":"2021","journal-title":"Rhinology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.imlet.2020.08.002","article-title":"Long-term omalizumab efficacy in allergic rhinitis","volume":"227","author":"Cavaliere","year":"2020","journal-title":"Immunol. Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.jaci.2020.05.032","article-title":"Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials","volume":"146","author":"Gevaert","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_47","first-page":"5249","article-title":"Effects of omalizumab therapy on allergic rhinitis: A pilot study","volume":"20","author":"Masieri","year":"2016","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.jaci.2017.11.051","article-title":"Efficacy and safety of dupilumab in perennial allergic rhinitis and comorbid asthma","volume":"142","author":"Weinstein","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1016\/S0140-6736(19)31881-1","article-title":"Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): Results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials","volume":"394","author":"Bachert","year":"2019","journal-title":"Lancet"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1016\/j.jaip.2021.01.031","article-title":"Indirect Treatment Comparison of Biologics in Chronic Rhinosinusitis with Nasal Polyps","volume":"9","author":"Peters","year":"2021","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.pop.2016.04.009","article-title":"Allergic Rhinitis","volume":"43","author":"Kakli","year":"2016","journal-title":"Prim. Care Clin. Off. Pract."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1007\/s11882-020-00977-7","article-title":"Mechanisms of Allergen Immunotherapy in Allergic Rhinitis","volume":"21","author":"Layhadi","year":"2021","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.jaci.2013.12.1088","article-title":"Mechanisms of allergen-specific immunotherapy: Multiple suppressor factors at work in immune tolerance to allergens","volume":"133","author":"Akdis","year":"2014","journal-title":"J. Allergy Clin. Immunol."}],"container-title":["Biomedicines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9059\/10\/10\/2486\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:46:53Z","timestamp":1760143613000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9059\/10\/10\/2486"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,5]]},"references-count":53,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["biomedicines10102486"],"URL":"https:\/\/doi.org\/10.3390\/biomedicines10102486","relation":{},"ISSN":["2227-9059"],"issn-type":[{"value":"2227-9059","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,5]]}}}