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Blood Т-cell subpopulations dynamics in asthma under suspended particulate load in vitro

https://doi.org/10.29413/ABS.2025-10.3.21

Abstract

Background. Bronchial asthma (BA) is characterized by dysregulation of the adaptive immune response. A significant contribution to pathological processes in urban environments is made by air pollution with solid suspended particles (HDPE). However, the expression of cytokine (interleukin (IL) 4, 6) and toll-like receptors (TLR) CD8+ cells in BA patients and their dynamics under exposure to atmospheric microtoxicants practically have not been studied.
The aim. To determine the features of expression of IL-4R, IL-6R, TLR2, and TLR4 in CD8+ cells in BA of varying severity and under the influence of solid suspended particles of atmospheric air.
Materials and methods. The study included 244 patients with asthma, 60 conditionally healthy individuals. Loading with simulated atmospheric suspensions was performed at a dose of 1 microgram (µg) of suspension per 1 ml of blood. The expression of IL-4R, IL-6R, TLR2, and TLR4 on CD8+ cells was analyzed by flow cytofluorometry. Statistical processing of the results was performed in the program “STATISTICA 10.0”. The critical significance level (p) for testing statistical hypotheses was assumed at p < 0.05.
Results. The main differences in cell signaling were observed between the group with partially controlled moderate BA and the control group. The expression of IL-4R is particularly strongly increased – by 217 % (p < 0.001), TLR4 – by 103 % (p < 0.001). The same group of patients is characterized by the greatest significance of differences in T-cytotoxic cells in comparison with the group of patients with mild bronchial asthma. IL-4 receptor expression on T-cytotoxic cells increased by 160 % (p < 0.001), TLR4 – by 108 % (p < 0.001).
Conclusion. The intensification of receptor expression is observed with an increase in the severity of the disease. The expression of IL-4R and TLR4 changes most intensively in T-cytotoxic cells IL-4R и TLR.

About the Authors

E. V. Kondratyeva
Vladivostok Branch of the Far Eastern Scientific Center of Physiology and Pathology of Respiration – Research Institute of Medical Climatology and Rehabilitation Treatment
Russian Federation

Elena V. Kondratyeva – Cand. Sc. (Biol.), senior researcher of Biomedical Research Laboratory 

Russkaya str., 73g, 690105 Vladivostok



T. I. Vitkina
Vladivostok Branch of the Far Eastern Scientific Center of Physiology and Pathology of Respiration – Research Institute of Medical Climatology and Rehabilitation Treatment
Russian Federation

Tatyana I. Vitkina –Dr. Sc. (Biol.), Professor of the RAS, Head of Medical Ecology and Recreational Resources Laboratory 

Russkaya str., 73g, 690105 Vladivostok



S. I. Kolesnikov
Scientific Сenter for Family Health and Human Reproduction Problems
Russian Federation

Sergey I. Kolesnikov – Dr. Sc. (Med.), professor, Member of the RAS, Senior Research Associate 

Timiryazeva str., 16, 664003 Irkutsk



References

1. GINA Report, Global Strategy for Asthma Management and Prevention; 2024: 263. URL: https://ginasthma.org/ [date of access: May 22, 2025].

2. Vitkina TI, Novgorodtseva TP, Kalinina EP, Lobanova EG, Antonyuk MV. Immune mechanisms for development of controlled and partially controlled asthma. Medical Immunology. 2019; 21(3): 495-502. (In Russ.). doi: 10.15789/1563-0625-2019-3-495-502

3. Bryant N, Muehling LM. T-cell responses in asthma exacerbations. Ann Allergy Asthma Immunol. 2022; 129(6): 709-718. doi: 10.1016/j.anai.2022.07.027

4. Keegan AD, Leonard WJ, Zhu J. Recent advances in understanding the role of IL-4 signaling. Fac Rev. 2021; 10: 71. doi: 10.12703/r/10-71

5. Han B, Li X, Ai RS, Deng SY, Ye ZQ, Deng X, et al. Atmospheric particulate matter aggravates cns demyelination through involvement of TLR-4/NF-kB signaling and microglial activation. Elife. 2022; 11: e72247. doi: 10.7554/eLife.72247

6. Luo W, Hu J, Xu W, Dong J. Distinct spatial and temporal roles for Th1, Th2, and Th17 cells in asthma. Front Immunol. 2022; 13: 974066. doi: 10.3389/fimmu.2022.974066

7. van der Ploeg EK, Krabbendam L, Vroman H, van Nimwegen M, de Bruijn MJW, de Boer GM, et al. Type-2 CD8+ T-cell formation relies on interleukin-33 and is linked to asthma exacerbations. Nat Commun. 2023; 14(1): 5137. doi: 10.1038/s41467-023-40820-x

8. Olsthoorn SEM, van Krimpen A, Hendriks RW, Stadhouders R. Chronic Inflammation in Asthma: Looking Beyond the Th2 Cell. Immunol Rev. 2025; 330(1): e70010. doi: 10.1111/imr.70010

9. Ni R, Su H, Burnett RT, Guo Y, Cheng Y. Long-term exposure to PM2.5 has significant adverse effects on childhood and adult asthma: A global meta-analysis and health impact assessment. One Earth. 2024; 7(11): 1953-1969. doi: 10.1016/j.oneear.2024.09.022

10. Veremchuk LV, Vitkina TI, Mineeva EE, Gvozdenko TA, Antonyuk MV, Sidletskaya KA, et al. Impact evaluation of environmental factors on respiratory function of asthma patients living in urban territory. Environmental Pollution. 2018; 235: 489-496. doi: 10.1016/j.envpol.2017.12.122

11. Vitkina TI, Sidletskaya KA. Diagnostic criteria for the progression of the chronic obstructive pulmonary disease under a high technogenic load. Hygiene and Sanitation. 2020; 99(2): 140-144. (In Russ.). doi: 10.33029/0016-9900-2020-99-2-140-144

12. Patent RU 2525427 МПК G 01 N 1/28; G 01 N 1/38. Method for preparing standard aerosol samples. Golokhvast KS, Panichev AM, Gulkov AN, Chaika VV. 7 p. 10.08.14, Bul. № 22. (In Russ.).

13. Sidletskaya K, Vitkina T, Denisenko Y. The role of toll-like receptors 2 and 4 in the pathogenesis of chronic obstructive pulmonary disease. International journal of chronic obstructive pulmonary disease. 2020; 15: 1481-1493. doi: 10.2147/COPD.S249131

14. Kondratyeva EV, Vitkina TI. Effects of atmospheric suspended solid particles on the immune system. Russian Open Medical Journal. 2024; 13(1): e0103. doi: 10.15275/rusomj.2024.0103

15. Wienhofer L, Marker M, Antoni AC, Sutter K, Sander A, Dudda M, et al. TLR4 Transactivates CD8+ T Lymphocytes upon Acute Sterile Tissue Injury. Immunohorizons. 2021; 5(5): 298-306. doi: 10.4049/immunohorizons.2100001

16. Sun Y, Xia T, Ma J, Sun Y. IL-12 Contributes to the Development of Asthma by Targeting HIF-1α/NLRP3 Pathway through Runx3. Int Arch Allergy Immunol. 2022; 183(12): 1231-1240. doi: 10.1159/000526803

17. Wu AY, Peebles RS. The emerging role of IL-23 in asthma and its clinical implications. Expert Rev Clin Immunol. 2023; 19(1): 1-5. doi: 10.1080/1744666X.2023.2125380

18. Sha JF, Xie QM, Chen N, Song SM, Ruan Y, Zhao CC, et al. TLR2-hif1α-mediated glycolysis contributes to pyroptosis and oxidative stress in allergic airway inflammation. Free Radic Biol Med. 2023; 200: 102-116. doi: 10.1016/j.freeradbiomed.2023.03.007

19. Zhang E, Ma Z, Li Q, Yan H, Liu J, Wu W, et al. TLR2 Stimulation Increases Cellular Metabolism in CD8+ T Cells and Thereby Enhances CD8+ T Cell Activation, Function, and Antiviral Activity. J Immunol. 2019; 203(11): 2872-2886. doi: 10.4049/jimmunol.1900065

20. Kurzweil V, LaRoche A, Oliver PM. Increased peripheral IL-4 leads to an expanded virtual memory CD8+ population. J Immunol. 2014; 192(12): 5643-51. doi: 10.4049/jimmunol.1301755

21. Yang R, Masters AR, Fortner KA, Champagne DP, Yanguas-Casas N, Silberger DJ, et al. IL-6 promotes the differentiation of a subset of naive CD8+ T cells into IL-21-producing B helper CD8+ T cells. J Exp Med. 2016; 213(11): 2281-2291. doi: 10.1084/jem.20160417

22. Bick F, Brenis Gomez CM, Lammens I, Van Moorleghem J, De Wolf C, Dupont S, et al. IL-2 family cytokines IL-9 and IL-21 differentially regulate innate and adaptive type 2 immunity in asthma. J Allergy Clin Immunol. 2024; 154(5): 1129-1145. doi: 10.1016/j.jaci.2024.07.024

23. Hinks TSC, Hoyle RD, Gelfand EW. CD8+ Tc2 cells: underappreciated contributors to severe asthma. Eur Respir Rev. 2019; 28(154): 190092. doi: 10.1183/16000617.0092-2019

24. Kondratyeva EV, Vitkina TI. Indicators of oxidative homeostasis and genotoxicity in patients with asthma under exposure to solid suspended atmospheric particulate matter. Bulletin Physiology and Pathology of Respiration. 2024; 94: 95-103. (In Russ.). doi: 10.36604/1998-5029-2024-94-95-103

25. Watterson TL, Sorensen J, Martin R, Coulombe RA Jr. Effects of PM2.5 collected from Cache Valley Utah on genes associated with the inflammatory response in human lung cells. J Toxicol Environ Health A. 2007; 70(20): 1731-44. doi: 10.1080/15287390701457746

26. Vitkina TI, Yankova VI, Gvozdenko TA, Nazarenko AV, Golokhvast KS, Kuznetsov VL, et al. The impact of multi-walled carbon nanotubes with different amount of metallic impurities on immunometabolic parameters in healthy volunteers. Food and Chemical Toxicology. 2016; 87: 138-147. doi: 10.1016/j.fct.2015.11.023

27. Zhang X, Zhong W, Meng Q, Lin Q, Fang C, Huang X, et al. Ambient PM2.5 exposure exacerbates severity of allergic asthma in previously sensitized mice. J Asthma. 2015; 52(8): 785-94. doi: 10.3109/02770903.2015.1036437

28. Zahedi A, Hassanvand MS, Jaafarzadeh N, Ghadiri A, Shamsipour M, Dehcheshmeh MG. Effect of ambient air PM2.5-bound heavy metals on blood metal(loid)s and children’s asthma and allergy pro-inflammatory (IgE, IL-4 and IL-13) biomarkers. J Trace Elem Med Biol. 2021; 68: 126826. doi: 10.1016/j.jtemb.2021.126826

29. Piao CH, Fan Y, Nguyen TV, Song CH, Kim HT, Chai OH. PM2.5 exposure regulates Th1/Th2/Th17 cytokine production through NF-κB signaling in combined allergic rhinitis and asthma syndrome. Int. Immunopharmacol. 2023; 119: 110254. doi: 10.1016/j.intimp.2023.110254

30. Li P, Wang J, Guo F, Zheng B, Zhang X. A novel inhibitory role of microRNA-224 in particulate matter 2.5-induced asthmatic mice by inhibiting TLR2. J Cell Mol Med. 2020; 24(5): 3040-3052. doi: 10.1111/jcmm.14940


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Kondratyeva E.V., Vitkina T.I., Kolesnikov S.I. Blood Т-cell subpopulations dynamics in asthma under suspended particulate load in vitro. Acta Biomedica Scientifica. 2025;10(3):201-207. https://doi.org/10.29413/ABS.2025-10.3.21

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