The role of epithelial alarmins and Th2 cytokines in the inflammatory response in allergic rhinitis
V. V. Makarevich,
A. D. Taganovich,
T. V. Mironova,
I. P. Shilovskiy,
M. R. Khaitov,
A. G. Kadushkin https://doi.org/10.18699/SSMJ20240504
Abstract
Allergic rhinitis (AR) occupies a leading position among the causes of morbidity throughout the world, to date, it has been diagnosed in 400 million people. In the formation and progression of AR, a significant role is assigned to cytokines associated with the second type of immune response, in particular, IL-4, IL-5, IL-9, IL-13, IL-25, IL-33, thymic stromal lymphopoietin (TSLP). This literature review provides information on the influence of the listed mediators on the structural cells of the nasal cavity and blood immune cells (T- and B-lymphocytes, eosinophils, macrophages, dendritic cells), and discusses their association with the manifestation of AR symptoms and the severity of the disease. The results of studies aimed at establishing the level of IL-4, IL-5, IL-9, IL-13, IL-25, IL-33 and TSLP in biological fluids (blood serum, nasal lavage) and their expression in nasal epithelial cells in patients with AR compared to healthy people are assessed.
Supporting agencies: The study was carried out within the framework of a joint assignment of the Belarusian Republican Foundation for Fundamental Research and the Russian Science Foundation (contract No. M23RNF-021, state registration No. 20230281).
About the Authors
V. V. Makarevich
Belarusian State Medical University of Minzdrav of the Republic of Belarus
Belarus
Belarus
Vasilina V. Makarevich
220083, Minsk, Dzerzhinskogo ave., 83
A. D. Taganovich
Belarusian State Medical University of Minzdrav of the Republic of Belarus
Belarus
Belarus
Anatoly D. Taganovich, doctor of medical sciences, professor
220083, Minsk, Dzerzhinskogo ave., 83
T. V. Mironova
Belarusian State Medical University of Minzdrav of the Republic of Belarus
Belarus
Belarus
Tatiana V. Mironova
220083, Minsk, Dzerzhinskogo ave., 83
I. P. Shilovskiy
National Research Center – Institute of Immunology of the Federal Medical-Biological Agency
Russian Federation
Russian Federation
Igor P. Shilovskiy, doctor of biological sciences
115522, Moscow, Kashirskoe highw., 24
M. R. Khaitov
National Research Center – Institute of Immunology of the Federal Medical-Biological Agency ; N.I. Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
Musa R. Khaitov, doctor of medical sciences, professor, corresponding member of RAS
115522, Moscow, Kashirskoe highw., 24
117997, Moscow, Ostrovityanova st., 1
A. G. Kadushkin
Belarusian State Medical University of Minzdrav of the Republic of Belarus
Belarus
Belarus
Aliaksei G. Kadushkin, doctor of medical sciences
220083, Minsk, Dzerzhinskogo ave., 83
References
1. Znamenskaya L.K., Shadchneva N.A., Panevskaya G.N. Dynamics of the incidence of allergic rhinitis in the adult population of the Republic of Crimea in the period from 2011 to 2015. Tavricheskiy medico-biologicheskiy vestnik = Tauric Medico-Biological Bulletin. 2017;20(3-3), 75–79. [In Russian].
2. Poroshina A.S., Shershakova N.N., Shilovskiy I.P., Kadushkin A.G., Taganovich A.D., Gudima G.O., Khaitov M.R. Role of IL-25, IL-33 and TSLP in the development of corticosteroid resistance. Immunologiya = Immunology. 2023;44(4):500–510. [In Russan]. doi: 10.33029/0206-4952-2023-44-4-500-510
3. Astafieva N.G., Baranov A.A., Vishneva E.A., Daikhes N.A., Zhestkov A.V., Ilyina N.I., Karneeva O.V., Karpova E.P., Kim I.A., Kryukov A.I., … Efendieva K.E. Allergic rhinitis. Clinical recommendations. Rossijskaya rinologiya = Russian Rhinology. 2020;28(4):246– 256. [In Russian]. doi: 10.17116/rosrino202028041246
4. Gusniev S.A., Polner S.A., Mikhaleva L.M., Ilina N.I., Esakova A.P., Kurbacheva O.M., Shilovskiy I.P., Khaitov M.R. Influence of interleukin-33 gene expression on clinical and morphological characteristics of the nasal mucosa in allergic rhinitis. Immunologiya = Immunology. 2021;42(1):68–79. [In Russan]. doi: 10.33029/0206-4952-2021-42-1-68-79
5. Azizova K.Sh., Abdurakhmanova N.R., Kurbanov A.G., Malakaeva Z.A., Davdieva A.A., Ismailova B.N., Mirzakhanov S.M., Mirzakhanov A.M. A study of comorbidity of bronchial asthma and allergic rhinitis in children. Mezhdunarodnyy nauchno-issledovatel’skiy zhurnal = International Research Journal. 2023;(1):69. [In Russan]. doi: 10.23670/IRJ.2023.127.54
6. Simbirtsev A.S. Cytokines and their role in immune pathogenesis of allergy. Rossiyskiy meditsinskiy zhurnal. Meditsinskoe obozrenie = Medical Journal of the Russian Federation. Medical Review. 2021;5(1):32–37. [In Russan]. doi: 10.32364/2587-6821-2021-5-1-32-37
7. Lloyd C.M., Snelgrove R.J. Type 2 immunity: Expanding our view. Sci. Immunol. 2018;3(25):eaat1604. doi: 10.1126/sciimmunol.aat1604
8. Nagarkar D.R., Poposki J.A., Comeau M.R., Biyasheva A., Avila P.C., Schleimer R.P., Kato A. Airway epithelial cells activate Th2 cytokine production in mast cells through IL-1 and thymic stromal lymphopoietin. J. Allergy Clin. Immunol. 2012;130(1):225–32.e4. doi: 10.1016/j.jaci.2012.04.019
9. Zhang K., Shan L., Rahman M.S., Unruh H., Halayko A.J., Gounni A.S. Constitutive and inducible thymic stromal lymphopoietin expression in human airway smooth muscle cells: role in chronic obstructive pulmonary disease. Am. J. Physiol. Lung Cell. Mol. Physiol. 2007;293(2):L375–L382. doi: 10.1152/ajplung.00045.2007
10. He R., Geha R.S. Thymic stromal lymphopoietin. Ann. N. Y. Acad. Sci. 2010;1183:13–24. doi: 10.1111/j.1749-6632.2009.05128.x
11. Svirshchevskaya E.V., Matushevskaya E.V., Chudakov D.B., Matushevskaya Yu.I. The role of infection in the pathogenesis of allergic dermatoses. Klinicheskaya dermatologiya i venerologiya = The Russian Journal of Dermatology and Venereology. 2015;14(2):4–10. [In Russan]. doi: 10.17116/klinderma20151424-10
12. Gushchin I.S. Eliminating the inevitability of an allergic response. Pulmonologiya = Pulmonology. 2010;(4):23–33. [In Russan]. doi: 10.18093/0869-0189-2010-4-23-33
13. Rebrova S.A. Allergic rhinitis: pathogenesis, diagnosis, treatment. Consilium Medicum. 2023;25(3):147–151. [In Russan]. doi: 10.26442/20751753.2023.3.202047
14. Whetstone C.E., Ranjbar M., Omer H., Cusack R.P., Gauvreau G.M. The role of airway epithelial cell alarmins in asthma. Cells. 2022;11(7):1105. doi: 10.3390/cells11071105
15. Campion N.J., Villazala-Merino S., Thwaites R.S., Stanek V., Killick H., Pertsinidou E., Zghaebi M., Toth J., Fröschl R., Perkmann T., … Eckl-Dorna J. Nasal IL-13 production identifies patients with late-phase allergic responses. J. Allergy Clin. Immunol. 2023;152(5):1167–1178.e12. doi: 10.1016/j.jaci.2023.06.026
16. Xu G., Zhang L., Wang D.Y., Xu R., Liu Z., Han D.M., Wang X.D., Zuo K.J., Li H.B. Opposing roles of IL-17A and IL-25 in the regulation of TSLP production in human nasal epithelial cells. Allergy. 2010;65(5):581–589. doi: 10.1111/j.1398-9995.2009.02252.x
17. Mou Z., Xia J., Tan Y., Wang X., Zhang Y., Zhou B., Li H., Han D. Overexpression of thymic stromal lymphopoietin in allergic rhinitis. Acta Otolaryngol. 2009;129(3):297–301. doi: 10.1080/00016480802225884
18. Kim D.W., Kim D.K., Eun K.M., Bae J.S., Chung Y.J., Xu J., Kim Y.M., Mo J.H. IL-25 could be involved in the development of allergic rhinitis sensitized to house dust mite. Mediators Inflamm. 2017;2017:3908049. doi: 10.1155/2017/3908049
19. Xu M., Dong C. IL-25 in allergic inflammation. Immunol. Rev. 2017;278(1):185–191. doi: 10.1111/imr.12558
20. Berezhnaya N.M. Interleukin 25 (IL-17E) helps allergy but fights cancer. Tsitokiny i vospalenie = Cytokines and Inflammation. 2010;9(3):3–14. [In Russian].
21. Liu D., Cao T., Wang N., Liu C., Ma N., Tu R., Min X. IL-25 attenuates rheumatoid arthritis through suppression of Th17 immune responses in an IL-13-dependent manner. Sci. Rep. 2016;6:36002. doi: 10.1038/srep36002
22. Fan H., Qin T.J., Ye L.S., Li F.T., Lin G.S., Liang Y.Q., Qu S.H. Expression of IL-25 and IL-33 and the count of EOS in peripheral blood of children with allergic rhinitis receiving immunotherapy. Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2018;32(6):443– 446. doi: 10.13201/j.issn.1001-1781.2018.06.011
23. Yang G., Zheng G., Zhang L., Zhu K., Xin W., Wei J. Expression level and significance of IL-17 and IL-23 in serum and nasal secretion of patients with allergic rhinitis and non-allergrie rhinitis. Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2015;29(12):1086–1090.
24. Moustafa H.S., Qotb M., Hussein M.A., Eid A., Ayad E.E., Fawzy T. Topical corticosteroids decrease IL-25 еxpression by immunohistochemistry. ORL J. Otorhinolaryngol. Relat. Spec. 2019;81(5-6):274–280. doi: 10.1159/000500990
25. Uchasova E.G., Gruzdeva O.V., Dyleva Yu.A., Karetnikova V.N. Interleukin-33 and fibrosis: pathogenesis updated. Meditsinskaya immunologiya = Medical Immunology. 2018;20(4):477–484. [In Russian]. doi: 10.15789/1563-0625-2018-4-477-484
26. Cayrol C., Girard J.P. Interleukin-33 (IL-33): A critical review of its biology and the mechanisms involved in its release as a potent extracellular cytokine. Cytokine. 2022;156:155891. doi: 10.1016/j.cyto.2022.155891
27. Clancy D.M., Sullivan G.P., Moran H.B.T., Henry C.M., Reeves E.P., McElvaney N.G., Lavelle E.C., Martin S.J. Extracellular neutrophil proteases are efficient regulators of IL-1, IL-33, and IL-36 cytokine activity but poor effectors of microbial killing. Cell Rep. 2018;22(11):2937–2950. doi: 10.1016/j.celrep.2018.02.062
28. Lefrançais E., Roga S., Gautier V., Gonzalez-de-Peredo A., Monsarrat B., Girard J.P., Cayrol C. IL-33 is processed into mature bioactive forms by neutrophil elastase and cathepsin G. Proc. Natl. Acad. Sci. USA. 2012;109(5):1673–1678. doi: 10.1073/pnas.1115884109
29. Heidarzadeh Arani M., Nikafarin S., Gilasi H. The relationship between serum level of interleukin-33 and allergic rhinitis and its severity in children. Iran. J. Pediatr. 2022;32(1):e105094. doi: 10.5812/ijp.105094
30. Kamekura R., Kojima T., Takano K., Go M., Sawada N., Himi T. The role of IL-33 and its receptor ST2 in human nasal epithelium with allergic rhinitis. Clin. Exp. Allergy. 2012;42(2):218–228. doi: 10.1111/j.1365-2222.2011.03867.x
31. Glück J., Rymarczyk B., Rogala B. Serum IL33 but not ST2 level is elevated in intermittent allergic rhinitis and is a marker of the disease severity. Inflamm. Res. 2012;61(6):547–50. doi: 10.1007/s00011-012-0443-9
32. Haccuria A., van Muylem A., Malinovschi A., Rasschaert J., Virreira M., Bruffaerts N., Hendrickx M., Michils A. Increased expression of IL-33 is found in the lower airways of patients with seasonal allergic rhinitis and is not related to natural allergen exposure. Clin. Exp. Allergy. 2021;51(6):845–848. doi: 10.1111/cea.13819
33. Sy C.B., Siracusa M.C. The therapeutic potential of targeting cytokine alarmins to treat allergic airway inflammation. Front. Physiol. 2016;7:214. doi: 10.3389/fphys.2016.00214
34. Mineev V.N., Sorokina L.N., Trofimov V.I., Nema M.A., Ivanov V.A. Interleukin-4 and interleukin-13 receptors: structure, function and genetic polymorphism. Pulmonologiya = Pulmonology. 2010;(3):113–119. [In Russian]. doi: 10.18093/0869-0189-2010-3-113-119
35. Stashkevich D.S., Filippova A.L., Burmistrova A.L. Actual issues of immunology: cytokine system, biological significance, genetic polymorphism, determination methods. Chelyabinsk: Tsitsero, 2016. [In Russian].
36. Gadani S.P., Cronk J.C., Norris G.T., Kipnis J. IL-4 in the brain: a cytokine to remember. J. Immunol. 2012;189(9):4213–4219. doi: 10.4049/jimmunol.1202246
37. Yarilin A.A. Immunology. Мoscow: GEOTAR-Me-dia, 2012. 752 p. [In Russian].
38. Kuzubova N.A., Titova O.N. T2-associated diseases: focus on the comorbid patient. Meditsinskiy sovet = Medical Council. 2020;(17):57–64. [In Russian]. doi: 10.21518/2079-701X-2020-17-57-64
39. Nur Husna S.M., Md Shukri N., Tuan Sharif S.E., Tan H.T.T., Mohd Ashari N.S., Wong K.K. IL-4/ IL-13 axis in allergic rhinitis: elevated serum cytokines levels and inverse association with tight junction molecules expression. Front. Mol. Biosci. 2022;9:819772. doi: 10.3389/fmolb.2022.819772
40. Tyurin Yu.A., Reshetnikova I.D., Sharifullina A.A., Agafonova E.V., Fassakhov R.S. Clinical and immunological features of patients with various forms of allergic rhinitis under sensitization by microbial, domestic and pollen allergens. Prakticheskaya meditsina = Practical Medicine. 2018;16(6):211–217. [In Russian].
41. Wang X.Q., Hu G.H., Kang H.Y., Shen Y., Ke X., Hong S.L. High frequency of T-helper type 9 cells in Chinese patients with allergic rhinitis. Asian Pac. J. Allergy Immunol. 2015;33(4):301–307. doi: 10.12932/AP0609.33.4.2015
42. Tataurshchikova N.S., Sidorovich I.G. The cytokine status as a criterion for the efficacy of intranasal aerosol therapy with the use of a cycloferon solution in the patients presenting with allergic rhinosinusitis. Vestnik otorinolaringologii = Bulletin of Otorhinolaryngology. 2012;(3):79–82. [In Russian].
43. Vlaykov A.N., Tacheva T.T., Vlaykova T.I., Stoyanov V.K. Serum and local IL-4, IL-5, IL-13 and immunoglobulin E in allergic rhinitis. Postepy Dermatol. Alergol. 2020;37(5):719–724. doi: 10.5114/ada.2020.100483
44. Badorrek P., Müller M., Koch W., Hohlfeld J.M., Krug N. Specificity and reproducibility of nasal biomarkers in patients with allergic rhinitis after allergen challenge chamber exposure. Ann. Allergy Asthma Immunol. 2017;118(3):290–297. doi: 10.1016/j.anai.2017.01.018
45. Rael E.L., Lockey R.F. Interleukin-13 signaling and its role in asthma. World Allergy Organ. J. 2011;4(3):54–64. doi: 10.1097/WOX.0b013e31821188e0
46. Roeb E. Interleukin-13 (IL-13)-A Pleiotropic Cytokine Involved in Wound Healing and Fibrosis. Int. J. Mol. Sci. 2023;24(16):12884. doi: 10.3390/ijms241612884
47. Kasaian M.T., Miller D.K. IL-13 as a therapeutic target for respiratory disease. Biochem. Pharmacol. 2008;76(2):147–155. doi: 10.1016/j.bcp.2008.04.002
48. Moore M.L., Peebles Jr. R.S. Interleukins Il5. In: Encyclopedia of respiratory medicine, 2006. P. 359–363. doi: 10.1016/B0-12-370879-6/00476-2
49. Kusano S., Kukimoto-Niino M., Hino N., Ohsawa N., Ikutani M., Takaki S., Sakamoto K., Hara-Yokoyama M., Shirouzu M., Takatsu K., Yokoyama S. Structural basis of interleukin-5 dimer recognition by it’s α receptor. Protein Sci. 2012;21(6):850–864. doi: 10.1002/pro.2072
50. Beketova T.V., Arseniev E.V. Interleukin-5 is a new target in the treatment of eosinophilic granulomatosis with polyangiitis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2020;58(3):321–329. [In Russian]. doi: 10.14412/1995-4484-2020-321-329
51. Kramer M.F., Ostertag P., Pfrogner E., Rasp G. Nasal interleukin-5, immunoglobulin E, eosinophilic cationic protein, and soluble intercellular adhesion molecule-1 in chronic sinusitis, allergic rhinitis, and nasal polyposis. Laryngoscope. 2000;110(6):1056–1062. doi: 10.1097/00005537-200006000-00031
52. Hoppenot D., Malakauskas K., Lavinskienė S., Bajoriūnienė I., Kalinauskaitė V., Sakalauskas R. Peripheral blood Th9 cells and eosinophil apoptosis in asthma patients. Medicina (Kaunas). 2015;51(1):10– 17. doi: 10.1016/j.medici.2015.01.001
53. Zheng N., Lu Y. Targeting the IL-9 pathway in cancer immunotherapy. Hum. Vaccin. Immunother. 2020;16(10):2333–2340. doi: 10.1080/21645515.2019.1710413
54. Putheti P., Awasthi A., Popoola J., Gao W., Strom T.B. Human CD4 memory T cells can become CD4+IL-9+ T cells. PLoS One. 2010;5(1):e8706. doi: 10.1371/journal.pone.0008706
55. Yazdani R., Shapoori S., Rezaeepoor M., Sanaei R., Ganjalikhani-Hakemi M., Azizi G., Rae W., Aghamohammadi A., Rezaei N. Features and roles of T helper 9 cells and interleukin-9 in immunological diseases. Allergol. Immunopathol. (Madr). 2019;47(1):90– 104. doi: 10.1016/j.aller.2018.02.003
56. Gounni A.S., Gregory B., Nutku E., Aris F., Latifa K., Minshall E., North J., Tavernier J., Levit R., Nicolaides N., Robinson D., Hamid Q. Interleukin-9 enhances interleukin-5 receptor expression, differentiation, and survival of human eosinophils. Blood. 2000;96(6):2163–2171
57. Allam A.A., Mansour S.A., Tarek A.E., Mohamed F.N., Morad E.A. The role of interleukin-9 in patients with allergic rhinitis. Egyptian Journal of Medical Microbiology. 2018;27(4):133–139. doi: 10.21608/ejmm.2018.285800
58. Nouri-Aria K.T., Pilette C., Jacobson M.R., Watanabe H., Durham S.R. IL-9 and c-Kit+ mast cells in allergic rhinitis during seasonal allergen exposure: effect of immunotherapy. J. Allergy Clin. Immunol. 2005;116(1):73–79. doi: 10.1016/j.jaci.2005.03.011
Review
For citations:
Makarevich V.V., Taganovich A.D., Mironova T.V., Shilovskiy I.P., Khaitov M.R., Kadushkin A.G. The role of epithelial alarmins and Th2 cytokines in the inflammatory response in allergic rhinitis. Сибирский научный медицинский журнал. 2024;44(5):35-45. (In Russ.) https://doi.org/10.18699/SSMJ20240504
Views:
875
Email this article 