Subpopulation and functional activity of regulatory T-lymphocytes in patients with chronic polyposis rhinosinusitis
https://doi.org/10.52485/19986173_2026_1_77
Abstract
Overcoming therapeutic resistance in chronic polypous rhinosinusitis (CRS) is directly linked to the recognition of its immunological heterogeneity. The modern paradigm views CRS as a spectrum of distinct endotypes (Th1, Th2, Th17), each requiring a specific targeted approach, making detailed immune profiling the cornerstone of personalized treatment strategies.
Objective. To study the numerical composition and functional activity of T-regulatory lymphocytes at different stages of differentiation depending on the immune response type in patients with chronic polypous rhinosinusitis.
Materials and Methods. The study included 44 patients suffering from chronic polypous rhinosinusitis. The control group consisted of 20 patients without chronic rhinosinusitis and concomitant pathology who underwent septoplasty. Using cluster analysis (k-means), all patients were divided into three clusters: 1st – patients with T helper 1 type immune response, 2nd – T helper 2 type, 3rd – T helper 17 type immune response. The content of Treg cells with the CD4+CD25hiCD127low phenotype in the venous blood of the subjects and the levels of cytokines (IL-2, IL-6, IL-10, TGF-β1, TNF-α) in blood serum and tissue homogenates were studied using the multiplex analysis system "Human Essential Immune Response Panel" by Biolegend (USA).
Results. The total number of Treg was increased in Th-2 and Th-1 immune responses, while it was minimal in the Th-17 response. The pool of naive Treg was preserved only in the Th-2 immune response. A progressive decrease in memory Treg was observed from the Th-1/Th-2 to the Th-17 response. Systemic disturbances in cytokine balance have been identified, explaining various mechanisms of pathogenesis of nasal polyps formation with different types of immune response.
Conclusion. Differences in the state of the immune regulatory system were established in patients with various immune endotypes of chronic polypous rhinosinusitis, manifested both at the level of cellular composition and the functional activity of T regulatory lymphocytes, which have a divergent nature depending on the CRS immune endotype. The concordance of changes in the cellular and cytokine profiles in peripheral blood and polyp tissue confirms the systemic nature of immunopathological disorders in CRS.
Keywords
About the Authors
T. M. ManikovskayaRussian Federation
Assistant
Department of Otolaryngology
672000; 39a Gorky St.; Chita
RSCI – AuthorID: 1175624
E. V. Egorova
Russian Federation
Doctor of Medical Sciences, Head of the Department
Department of Otolaryngology
672000; 39a Gorky St.; Chita
RSCI – AuthorID: 769223
E. V. Fefelova
Russian Federation
Doctor of Medical Sciences, Associate Professor, Professor
Department of Pathological Physiology
672000; 39a Gorky St.; Chita
RSCI – AuthorID: 520408
P. P. Tereshkov
Russian Federation
Candidate of Medical Sciences, Head of the Laboratory
Research Institute of Molecular Biology; Laboratory of Experimental and
Clinical Biochemistry and Immunology
672000; 39a Gorky St.; Chita
RSCI - AuthorID: 520402
N. N. Tsybikov
Russian Federation
Doctor of Medical Sciences, Professor, Head of the Department
Department of Pathophysiology
672000; 39a Gorky St.; Chita
RSCI – AuthorID: 520407
References
1. Bachert C., Han J.K., Wagenmann M., et al. EUFOREA expert board meeting on uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) and biologics: Definitions and management. J Allergy Clin Immunol. 2021 Jan. 147 (1). 29–36. doi: 10.1016/j.jaci.2020.11.013.
2. Ivanov M.O., Maksimenya M.V., Karavaeva T.M., et al. Clinical and some biochemical features of rhinosinusitis of various etiologies. Vestnik otorinolaringologii. 2019. 84 (3). 41–45. (in Russian).
3. Zahran A.M., El-Badaway O., Elsayh I.K.I., Osman M.M. Delineation of T cell subsets in chronic rhinosinusitis with nasal polyps. Acta Otorhinolaryngol Ital. 2022 Oct. 42 (5). 441–449. doi: 10.14639/0392-100X-N2023.
4. Xu Z., Huang Y., Meese T., et al. The multi-omics single-cell landscape of sinus mucosa in uncontrolled severe chronic rhinosinusitis with nasal polyps. Clin Immunol. 2023 Nov. 256. 109791. doi: 10.1016/j.clim.2023.109791.
5. Toppila-Salmi S., Reitsma S., Hox V., et al. Endotyping in Chronic Rhinosinusitis-An EAACI Task Force Report. Allergy. 2025 Jan. 80 (1). 132–147. doi: 10.1111/all.16418.
6. Koh C.H., Lee S., Kwak M., Kim B.S., Chung Y. CD8 T-cell subsets: heterogeneity, functions, and therapeutic potential. Exp Mol Med. 2023 Nov. 55 (11). 2287–2299. doi: 10.1038/s12276-023-01105-x.
7. Seder R.A., Ahmed R. Similarities and differences in CD4+ and CD8+ effector and memory T cell generation. Nat Immunol. 2003 Sep. 4(9). 835-842. doi: 10.1038/ni969.
8. Zebley C.C., Akondy R.S., Youngblood B.A., Kissick H.T. Defining the Molecular Hallmarks of T-Cell Memory. Cold Spring Harb Perspect Biol. 2022 Mar. 1. 14 (3). a037804. doi: 10.1101/cshperspect.a037804.
9. Lei C., Jiang J., Zhang Y., Xiong G. Role and Function of Regulatory T Cell in Chronic Rhinosinusitis with Nasal Polyposis. J Immunol Res. 2022 Mar. 26. 2022. 1144563. doi: 10.1155/2022/1144563.
10. Dong D., Sindhava V.J., Ganesan A., et al. Normal Treg homeostasis and suppressive function require both FOXP1 and FOXP4. JCI Insight. 2025 Aug. 12. 10 (18). e195981. doi: 10.1172/jci.insight.195981.
11. Xu Z., Li R., Wang L., et al. Pathogenic role of different phenotypes of immune cells in airway allergic diseases: a study based on Mendelian randomization. Front Immunol. 2024 May 15. 15. 1349470. doi: 10.3389/fimmu.2024.1349470.
12. Huang Y., Yan B., Meng C., Zhang L., Wang C. Matrix metalloproteinases in chronic rhinosinusitis. Expert Rev Clin Immunol. 2024 May. 20 (5). 547–558. doi: 10.1080/1744666X.2024.2302362.
13. Calus L., Van Bruaene N., Bosteels C., et al. Twelve-year follow-up study after endoscopic sinus surgery in patients with chronic rhinosinusitis with nasal polyposis. Clin Transl Allergy. 2019 Jun. 14. 9. 30. doi: 10.1186/s13601-019-0269-4.
14. Huang Y., Zhang N., Xu Z., Zhang L., Bachert C. The Development of the Mucosal Concept in Chronic Rhinosinusitis and Its Clinical Implications. J Allergy Clin Immunol Pract. 2022 Mar. 10 (3). 707–715. doi: 10.1016/j.jaip.2021.10.054.
15. So K., Bertolini T.B., Krishnan P., et al. Distinct functions and transcriptional signatures in orally induced regulatory T cell populations. Front Immunol. 2023 Oct. 26. 14. 1278184. doi: 10.3389/fimmu.2023.1278184.
16. Zhu S., Zhou N., Li Q., Liu X. Rewiring immune suppression in NSCLC: Roles and plasticity of Tregs and Th17 cells. Front Immunol. 2025 Oct. 16. 16. 1658848. doi: 10.3389/fimmu.2025.1658848.
17. Saxena V., Lienesch D.W., Zhou M., et al. Dual roles of immunoregulatory cytokine TGF-beta in the pathogenesis of autoimmunity-mediated organ damage. J Immunol. 2008 Feb. 1. 180 (3). 1903-1912. doi: 10.4049/jimmunol.180.3.1903.
18. Koh C.H., Kim B.S., Kang C.Y., Chung Y., Seo H. IL-17 and IL-21: Their Immunobiology and Therapeutic Potentials. Immune Netw. 2024 Jan. 19. 24 (1). e2. doi: 10.4110/in.2024.24.e2.
19. Kim H.S., Jang S.W., Lee W., et al. PTEN drives Th17 cell differentiation by preventing IL-2 production. J Exp Med. 2017 Nov 6. 214 (11). 3381–3398. doi: 10.1084/jem.20170523.
20. Dienz O., Rincon M. The effects of IL-6 on CD4 T cell responses. Clin Immunol. 2009 Jan. 130 (1). 27–33. doi: 10.1016/j.clim.2008.08.018.
21. Yoshida H., Magi M., Tamai H., et al. Effects of interleukin-6 signal inhibition on Treg subpopulations and association of Tregs with clinical outcomes in rheumatoid arthritis. Rheumatology. 2024 Sep. 1. 63 (9). 2515–2524. doi: 10.1093/rheumatology/keae196.
22. Aliyu M., Zohora F.T., Anka A.U., et al. Interleukin-6 cytokine : An overview of the immune regulation, immune dysregulation, and therapeutic approach. Int Immunopharmacol. 2022 Oct. 111. 109130. doi: 10.1016/j.intimp.2022.109130.
23. Smirnova O.V., Sinyakov A.A. Immunity in chronic rhinosinusitis and comorbid conditions. Rossiiskii immunologicheskii zhurnal. 2024. 27 (3). 635–642. doi: 10.46235/1028-7221-16682-IIC. (in Russian).
24. Laidlaw T.M., Mullol J., Woessner K.M., Amin N., Mannent L.P. Chronic Rhinosinusitis with Nasal Polyps and Asthma. J Allergy Clin Immunol Pract. 2021 Mar. 9 (3). 1133–1141. doi: 10.1016/j.jaip.2020.09.063.
25. Bachert C., Luong A.U., Gevaert P., et al. The Unified Airway Hypothesis: Evidence From Specific Intervention With Anti-IL-5 Biologic Therapy. J Allergy Clin Immunol Pract. 2023 Sep. 11 (9). 2630–2641. doi: 10.1016/j.jaip.2023.05.011.
Review
For citations:
Manikovskaya T.M., Egorova E.V., Fefelova E.V., Tereshkov P.P., Tsybikov N.N. Subpopulation and functional activity of regulatory T-lymphocytes in patients with chronic polyposis rhinosinusitis. Transbaikalian Medical Bulletin. 2026;(1):77-90. (In Russ.) https://doi.org/10.52485/19986173_2026_1_77
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