astmedАстраханский медицинский журналAstrakhan medical journal1992-6499ФГБОУ ВО Астраханский ГМУ Минздрава России10.17021/1992-6499-2024-2-27-36astmed-438Research ArticleНАУЧНЫЕ ОБЗОРЫSCIENTIFIC REVIEWSВлияние гипоксии на клетки иммунной системыImpact of hypoxia on the immune systemИгнатенкоГ. А.IgnatenkoG. A.

Григорий Анатольевич Игнатенко, доктор медицинских наук, профессор, заведующий кафедрой пропедевтики внутренних болезней, ректор

Донецк

Grigoriy A. Ignatenko, Dr. Sci. (Med.), Professor, Head of the Department, Rector

Donetsk

gai-1959@mail.ruПрилуцкийА. С.PrilutskiyA. S.

Александр Сергеевич Прилуцкий, доктор медицинских наук, профессор кафедры микробиологии, вирусологии, иммунологии и аллергологии

Донецк

Aleksandr S. Prilutskiy, Dr. Sci. (Med.), Professor

Donetsk

aspr@mail.ruБондаренкоН. Н.BondarenkoN. N.

Надежда Николаевна Бондаренко, доктор медицинских наук, профессор, заведующая кафедрой физиологии с лабораторией теоретической и прикладной нейрофизиологии имени академика В. Н. Казакова

Донецк

Nadezhda N. Bondarenko, Dr. Sci. (Med.), Professor, Head of the Department

 Donetsk

nanibo50@mail.ruПрилуцкаяО. А.PrilutskayaO. A.

Ольга Александровна Прилуцкая, кандидат медицинских наук, доцент кафедры внутренних болезней № 4

Донецк

Olga A. Prilutskaya, Сand. Sci. (Med.), Associate Professor

Donetsk

set1999@mail.ruДубоваяА. В.DubovayaA. V.

Анна Валериевна Дубовая, доктор медицинских наук, профессор, заведующая кафедрой педиатрии № 3

Донецк

Anna V. Dubovaya, Dr. Sci. (Med.), Professor, Head of the Department

Donetsk

dubovaya_anna@mail.ruТолстойВ. А.TolstoyV. A.

Виталий Аркадьевич, кандидат медицинских наук, доцент, доцент кафедры пропедевтики внутренних болезней 

Донецк

Vitaliy A. Tolstoy, Cand. Sci. (Med.), Associate Professor

Donetsk

tolstoy_vitaliy@mail.ruКалугаА. А.KalugaA. A.

Александр Александрович Калуга, А. А. Калуга, ассистент кафедры терапии, факультет интернатуры и последипломного образования имени профессора А. И. Дядыка

Донецк

Aleksandr A. Kaluga, Assistant

Donetsk

fpodnmu@yandex.ruДонецкий государственный медицинский университет имени М. ГорькогоРоссияDonetsk State Medical University named after M. GorkyRussian Federation2024170720241922736Copyright © Игнатенко Г.А., Прилуцкий А.С., Бондаренко Н.Н., Прилуцкая О.А., Дубовая А.В., Толстой В.А., Калуга А.А., 20242024Игнатенко Г.А., Прилуцкий А.С., Бондаренко Н.Н., Прилуцкая О.А., Дубовая А.В., Толстой В.А., Калуга А.А.Ignatenko G.A., Prilutskiy A.S., Bondarenko N.N., Prilutskaya O.A., Dubovaya A.V., Tolstoy V.A., Kaluga A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.astmedj.ru/jour/article/view/438

Гипоксия – это состояние, возникающее при понижении нормального уровня кислорода из-за снижения доступности или доставки этого газа к клеткам и тканям. Гипоксические состояния возникают при многих заболеваниях, при низком содержании кислорода в тканях и клетках происходят многочисленные физиологические и патологические изменения. Обобщены сведения научной литературы о влиянии гипоксии на иммунную систему. Проведенный анализ показывает, что недостаток кислорода оказывает на регуляцию иммунного ответа существенное влияние, которое опосредуется семейством факторов, индуцируемых гипоксией. Среди них наиболее изученным является HIF-1α. Действие факторов осуществляется различными механизмами. При этом влияние индуцированных гипоксией факторов зарегистрировано при анализе функции всех клеток как естественного, так и приобретенного иммунитета.

Hypoxia is a condition that occurs when there is a decrease in the normal level of oxygen due to a decrease in the availability or delivery of this gas to cells and tissues. It is important to note that hypoxic conditions occur in many diseases. With a low oxygen content in tissues and cells, numerous physiological and pathological changes occur. The article summarizes information from the scientific literature on the effect of hypoxia on the immune system. The analysis shows that the lack of oxygen has a significant effect on the regulation of the immune response. This influence is mediated by a family of factors induced by hypoxia. Among them, the most studied is HIF-1α. The action of factors is carried out by various mechanisms. The influence of factors induced by hypoxia was registered in the analysis of the function of all cells of natural and acquired immunity.

гипоксияболезниклеткииммунитетврожденныйприобретенныйаллергияфакторыиндуцируемые гипоксиейhypoxiadiseasescellsimmunitycongenitalacquiredallergyfactors induced by hypoxiaАвторы декларируют отсутствие внешнего финансирования для проведения исследования и публикации статьи.The authors declare that there is no external funding for the exploration and analysis work.ReferencesCassavaugh J., Lounsbury K. M. Hypoxia-mediated biological control // Journal of Cellular Biochemistry. 2011. Vol. 112, no. 3. P. 735–744. doi: 10.1002/jcb.22956.Cassavaugh J., Lounsbury K. M. Hypoxia-mediated biological control. Journal of Cellular Biochemistry. 2011; 112 (3): 735–744. doi: 10.1002/jcb.22956.Игнатенко Г. А., Дубовая А. В., Науменко Ю. В. Возможности применения нормобарической гипокситерапии в терапевтической и педиатрической практиках // Российский вестник перинатологии и педиатрии. 2022. Т. 67, № 6. С. 46–53.Ignatenko G. A., Dubovaya A. V., Naumenko Ju. V. Treatment potential of normobaric hypoxic therapy in therapeutic in pediatric practice. Rossiyskiy vestnik perinatologii i pediatrii = Russian Bulletin of Perinatology and Pediatrics. 2022; 6 (67): 46–53. (in Russ.).Rhim T., Lee D. Y., Lee M. Hypoxia as a target for tissue specific gene therapy // Journal of Controlled Release. 2013. Vol. 172, no. 2. P. 484–494. doi: 10.1016/j.jconrel.2013.05.021.Rhim T., Lee D. Y., Lee M. Hypoxia as a target for tissue specific gene therapy. Journal of Controlled Release. 2013; 172 (2): 484–494. doi: 10.1016/j.jconrel.2013.05.021.Doutreleau S. Physiological and pathological responses to altitude // Revue-des-Maladies-Respiratoires. 2021. Vol. 38, no. 10. P. 1013–1024. doi: 10.1016/j.rmr.2020.12.007.Doutreleau S. Physiological and pathological responses to altitude. Revue-des-Maladies-Respiratoires. 2021: 38 (10): 1013–1024. doi: 10.1016/j.rmr.2020.12.007.Игнатенко Г. А., Мухин И. В., Гавриляк В. Г., Чеботарева Е. Н., Дзюбан А. С., Паниева Н. Ю., Паниев Д. С. Гипокси-гиперокситерапия в лечении больных коморбидной кардиальной патологией // Университетская клиника. 2019. № 1 (30). С. 5–10.Ignatenko G. A., Mukhin I. V., Gavrilyak V. G., Chebotareva E. N., Dzyuban A. S., Panieva N. Yu., Paniev D. S. Hypoxia Hyperoxitherapy in the treatment of patients with comorbid cardiac pathology. Universitetskaya klinika = University Clinic. 2019; 1 (30): 5–10. (in Russ.).Игнатенко Г. А., Денисова Е. М., Сергиенко Н. В. Гипокситерапия как перспективный метод повышения эффективности комплексного лечения коморбидной патологии // Вестник неотложной и восстановительной хирургии. 2021. Т. 6, № 4. С. 73–80.Ignatenko G. A., Denisova E. M., Sergienko N. V. Hypoxiterapy as prospective method of increasing the effectiveness of complex treatment of comorbid pathology. Vestnik neotlozhnoy i vosstanovitel'noy khirurgii = Bulletin of Urgent and Recovery Surgery. 2021; 4 (6): 73–80. (in Russ.).Игнатенко Г. А., Майлян Э. А., Игнатенко Т. С., Капанадзе Г. Д. Влияние гипокситерапии на содержание аутоантител к антигенам щитовидной железы у женщин с аутоиммунным тиреоидитом // Медико-социальные проблемы семьи. 2022. Т. 27, № 3. С. 46–51.Ignatenko G. A., Maylyan E.A., Ignatenko T. S., Kapanadze G. D. The influence of hypoxitherapy on the content of autoantibodies to thyroid antigens in women with autoimmune thyroiditis. Mediko-sotsial'nye problemy sem'I = Medical and Social Problems of Family. 2022; 3 (27): 46–51. (in Russ.).Choudhry H., Harris A. L. Advances in Hypoxia Inducible Factor Biology // Cell Metabolism. 2018. Vol. 27, no. 2. P. 281–298. doi: 10.1016/j.cmet.2017.10.005.Choudhry H., Harris A. L. Advances in Hypoxia Inducible Factor Biology. Cell Metabolism. 2018; 27 (2): 281– 298. doi: 10.1016/j.cmet.2017.10.005.Hsu T.-S., Lin Y.-L., Wang Yu-An, Mo S.-T., Chi Po-Yu, Lai A. C.-Y., Pan H.-Y., Chang Ya-J., Lai M.-Z. HIF-2α is indispensable for regulatory T cell function // Nature Communications. 2020. Vol. 11, no. 1. P. 5005. doi: 10.1038/s41467-020-18731-y.Hsu T.-S., Lin Y.-L., Wang Yu-An, Mo S.-T., Chi Po-Yu, Lai A. C.-Y., Pan H.-Y., Chang Ya-J., Lai M.-Z. HIF-2α is indispensable for regulatory T cell function. Nature Communications. 2020; 11 (1): 5005. doi: 10.1038/s41467-020-18731-y.Wu D., Xu J., Jiao W., Liu L., Yu J., Zhang M., Chen G. Suppression of Macrophage Activation by Sodium Danshensu via HIF-1α/STAT3 / NLRP3 Pathway Ameliorated Collagen-Induced Arthritis in Mice // Molecules. 2023. Vol. 28, no. 4. P. 551. doi: 10.3390/molecules28041551.Wu D., Xu J., Jiao W., Liu L., Yu J., Zhang M., Chen G. Suppression of Macrophage Activation by Sodium Danshensu via HIF-1α/STAT3/NLRP3 Pathway Ameliorated Collagen-Induced Arthritis in Mice. Molecules. 2023; 28 (4): 551. doi: 10.3390/molecules28041551.Li Y., Zhang M.-Z., Zhang S.-J., Sun X., Zhou C., Li J., Liu J., Feng J., Lu S.-Y., Pei-Jun L., Wang Ji-C. HIF1α inhibitor YC-1 suppresses triple-negative breast cancer growth and angiogenesis by targeting PlGF/VEGFR1-induced macrophage polarization // Biomedicine & Pharmacotherapy. 2023. Vol. 161. P. 114423. doi: 10.1016/j.biopha.2023.114423.Li Y., Zhang M.-Z., Zhang S.-J., Sun X., Zhou C., Li J., Liu J., Feng J., Lu S.-Y., Pei-Jun L., Wang Ji-C. HIF1α inhibitor YC-1 suppresses triple-negative breast cancer growth and angiogenesis by targeting PlGF/VEGFR1-induced macrophage polarization. Biomedicine & Pharmacotherapy. 2023; 161: 114423. doi: 10.1016/j.biopha.2023.114423.Mancino A., Schioppa T., Larghi P., Pasqualini F., Nebuloni M., Chen I.-H., Sozzani S., Austyn J. M., Mantovani A., Sica A. Divergent effects of hypoxia on dendritic cell functions // Blood. 2008. No. 112. Р. 3723–3734.Mancino A., Schioppa T., Larghi P., Pasqualini F., Nebuloni M., Chen I.-H., Sozzani S., Austyn J. M., Mantovani A., Sica A. Divergent effects of hypoxia on dendritic cell functions. Blood. 2008; 112: 3723–3734.Qu J., Li D., Jin J., Sun N., Wu J., Yang C., Wu L., Zhuang S., Wu H., Chen R., Ren Y., Zhong C., Ying L., Zhang Y., Yuan X., Zhang M. Hypoxia-Inducible Factor 2α Attenuates Renal Ischemia-Reperfusion Injury by Suppressing CD36-Mediated Lipid Accumulation in Dendritic Cells in a Mouse Model // Journal of the American Society of Nephrology. 2023. Vol. 34, no. 1. P. 73–87. doi: 10.1681/ASN.0000000000000027.114423.Qu J., Li D., Jin J., Sun N., Wu J., Yang C., Wu L., Zhuang S., Wu H., Chen R., Ren Y., Zhong C., Ying L., Zhang Y., Yuan X., Zhang M. Hypoxia-Inducible Factor 2α Attenuates Renal Ischemia-Reperfusion Injury by Suppressing CD36-Mediated Lipid Accumulation in Dendritic Cells in a Mouse Model. Journal of the American Society of Nephrology. 2023; 34 (1): 73–87. doi: 10.1681/ASN.0000000000000027.114423.Wang G. L., Jiang B. H., Rue E. A., Semenza G. L. Hypoxia-inducible factor 1 is a basic-helix-loop-helixPAS heterodimer regulated by cellular O2 tension // Proceedings of the National Academy of Sciences USA. 1995. Vol. 92, no. 12. P. 5510–5514. doi: 10.1073/pnas.92.12.5510.114423.Wang G. L, Jiang B. H., Rue E. A., Semenza G. L. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proceedings of the National Academy of Sciences USA. 1995; 92 (12): 5510–5514. doi: 10.1073/pnas.92.12.5510.114423.Loboda A., Jozkowicz A., Dulak J. HIF-1 versus HIF-2–is one more important than the other? // Vascular Pharmacology. 2012. Vol. 56, no. 5–6. P. 245–251. doi: 10.1016/j.vph.2012.02.006.Loboda A., Jozkowicz A., Dulak J. HIF-1 versus HIF-2–is one more important than the other? Vascular Pharmacology. 2012; 56 (5–6): 245–251. doi: 10.1016/j.vph.2012.02.006.Burrows N., Bashford-Rogers R. J. M., Bhute V. J., Peñalver A., Ferdinand J. R., Stewart B. J., Smith J. E. G., Deobagkar-Lele M., Giudice G., Connor T. M., Inaba A., Bergamaschi L., Smith S., Tran M. G. B., Petsalaki E., Lyons P. A., Espeli M., Huntly B. J. P., Smith K. G. C., Cornall R. J., Clatworthy M. R., Maxwell P. H. Dynamic regulation of hypoxia-inducible factor-1α activity is essential for normal b cell development // Nature Immunology. 2020. Vol. 21, no. 11. P. 1408–1420. doi: 10.1038/s41590-020-0772-8.Burrows N., Bashford-Rogers R. J. M., Bhute V. J., Peñalver A., Ferdinand J. R., Stewart B. J., Smith J. E. G., Deobagkar-Lele M., Giudice G., Connor T. M., Inaba A., Bergamaschi L., Smith S., Tran M. G. B., Petsalaki E., Lyons P. A., Espeli M., Huntly B. J. P., Smith K. G. C., Cornall R. J., Clatworthy M. R., Maxwell P. H. Dynamic regulation of hypoxia-inducible factor-1α activity is essential for normal b cell development. Nature Immunology. 2020; 21 (11): 1408–1420. doi: 10.1038/s41590-020-0772-8.Cho S. H., Raybuck A. L., Stengel K., Wei M., Beck T. C., Volanakis E., Thomas J. W., Hiebert S., Haase V. H., Boothby M. R. Germinal centre hypoxia and regulation of antibody qualities by a hypoxia response system // Nature. 2016. Vol. 537, no. 7619. P. 234–238. doi: 10.1038/nature19334.Cho S. H., Raybuck A. L., Stengel K., Wei M., Beck T. C., Volanakis E., Thomas J. W., Hiebert S., Haase V. H., Boothby M. R. Germinal centre hypoxia and regulation of antibody qualities by a hypoxia response system. Nature. 2016; 537 (7619): 234–238. doi: 10.1038/nature19334.Li L., Feng C., Qin J., Li D., Liu M., Han S., Zheng B. Regulation of humoral immune response by HIF-1αdependent metabolic reprogramming of the germinal center reaction // Cell Immunology. 2021. Vol. 367, no. 104409. P. 1–14. doi: 10.1016/j.cellimm.2021.104409.17.Li L., Feng C., Qin J., Li D., Liu M., Han S., Zheng B. Regulation of humoral immune response by HIF-1αdependent metabolic reprogramming of the germinal center reaction. Cell Immunology. 2021; 367 (104409): 1–14. doi: 10.1016/j.cellimm.2021.104409.17.Cho H. S., Raybuck A. L., Blagih J., Kemboi E., Haase V. H., Jones R. G., Boothby M. R. Hypoxia-inducible factors in CD4+ T cells promote metabolism, switch cytokine secretion, and T cell help in humoral immunity // Proceedings of the National Academy of Sciences of the United States of America. 2019. Vol. 116. P. 8975–8984. doi: 10.1073/pnas.1811702116.Cho H. S., Raybuck A. L., Blagih J., Kemboi E., Haase V. H., Jones R. G., Boothby M. R. Hypoxia-inducible factors in CD4+ T-cells promote metabolism, switch cytokine secretion, and T cell help in humoral immunity. Proceedings of the National Academy of Sciences of the United States of America. 2019; 116: 8975–8984. doi: 10.1073/pnas.1811702116.Suthen S., Lim C.-J., Nguyen P. H. D., Dutertre C.-A., Lai H. L. H., Wasser M., Chua C., Lim T. K. H., Leow W. O., Loh T. J., Wan W. K., Pang Y. H., Soon G., Cheow P. C., Kam J. H., Iyer S., Kow A., Tam W. L., Shuen T. W. H., Toh H. C., Dan Y. Y., Bonney G. K., Chan C. Y., Chung A., Goh B. K. P., Zhai W., Ginhoux F., Chow P. K. H., Albani S., Chew V. Hypoxia-driven immunosuppression by Treg and type-2 conventional dendritic cells in HCC // Hepatology. 2022. Vol. 76, no. 5. P. 1329–1344. doi: 10.1002/hep.32419.Suthen S., Lim C.-J., Nguyen P. H. D., Dutertre C.-A., Lai H. L. H., Wasser M., Chua C., Lim T. K. H., Leow W. O., Loh T. J., Wan W. K., Pang Y. H., Soon G., Cheow P. C., Kam J. H., Iyer S., Kow A., Tam W. L., Shuen T. W. H., Toh H. C., Dan Y. Y., Bonney G. K., Chan C. Y., Chung A., Goh B. K. P., Zhai W., Ginhoux F., Chow P. K. H., Albani S., Chew V. Hypoxia-driven immunosuppression by Treg and type-2 conventional dendritic cells in HCC. Hepatology. 2022; 76 (5): 1329–1344. doi: 10.1002/hep.32419.Groneberg M., Hoenow S., Marggraff C., Fehling H., Metwally N. G., Hansen C., Bruchhaus I., Tiegs G., Sellau J., Lotter H. HIF-1α modulates sex-specific Th17/Treg responses during hepatic amoebiasis // Journal of Hepatology. 2022. Vol. 76, no. 1. P. 160–173. doi: 10.1016/j.jhep.2021.09.020.Groneberg M., Hoenow S., Marggraff C., Fehling H., Metwally N. G., Hansen C., Bruchhaus I., Tiegs G., Sellau J., Lotter H. HIF-1α modulates sex-specific Th17/Treg responses during hepatic amoebiasis. Journal of Hepatology. 2022; 76 (1): 160–173. doi: 10.1016/j.jhep.2021.09.020.Flück K., Breves G., Fandrey J., Winning S. Hypoxia-inducible factor 1 in dendritic cells is crucial for the activation of protective regulatory T cells in murine colitis // Mucosal Immunology. 2016. Vol. 9, no. 2. P. 379–390. doi: 10.1038/mi.2015.67.Flück K., Breves G., Fandrey J., Winning S. Hypoxia-inducible factor 1 in dendritic cells is crucial for the activation of protective regulatory T cells in murine colitis. Mucosal Immunology. 2016; 9 (2): 379–390. doi: 10.1038/mi.2015.67.Feldhoff L. M., Rueda C. M., Moreno-Fernandez M. E., Sauer J., Jackson C. M., Chougnet C. A., Rupp J. IL-1β induced HIF-1α inhibits the differentiation of human FOXP3+ T-cells // Scientific Reports. 2017. Vol. 7, no. 1. P. 465. doi: 10.1038/s41598-017-00508-x.Feldhoff L. M., Rueda C. M., Moreno-Fernandez M. E., Sauer J., Jackson C. M., Chougnet C. A., Rupp J. IL1β induced HIF-1α inhibits the differentiation of human FOXP3+ T cells. Scientific Reports. 2017; 7 (1): 465. doi: 10.1038/s41598-017-00508-x.Wang H., Flach H., Onizawa M., Wei L., McManus M. T., Weiss A. Negative regulation of Hif1a expression and TH17 differentiation by the hypoxia-regulated microRNA miR-210 // Nature Immunology. 2014. Vol. 15, no. 4. P. 393–401. doi: 10.1038/ni.2846.Wang H., Flach H., Onizawa M., Wei L., McManus M. T., Weiss A. Negative regulation of Hif1a expression and TH17 differentiation by the hypoxia-regulated microRNA miR-210. Nature Immunology. 2014; 15 (4): 393–401. doi: 10.1038/ni.2846.Talreja J.,Talwar H., Bauerfeld C., Grossman L. I., Zhang K., Tranchida P., Samavati L. HIF-1α regulates IL-1β and IL-17 in sarcoidosis // Elife. 2019. No. 8. P.e44519. doi: 10.7554/eLife.44519.Talreja J.,Talwar H., Bauerfeld C., Grossman L. I., Zhang K., Tranchida P., Samavati L. HIF-1α regulates IL1β and IL-17 in sarcoidosis. Elife. 2019; 8: e44519. doi: 10.7554/eLife.44519.Jianjun Y., Zhang R., Lu G., Shen Y., Peng L., Zhu C., Cui M., Wang W., Arnaboldi P., Tang M., Gupta M., Qi C.-F., Jayaraman P., Zhu H., Jiang B., Chen S.-h., He J. C., Ting A. T., Zhou M.-M., Kuchroo V. K., Morse 3rd H. C., Ozato K., Sikora A. G., Xiong H. T cell-derived inducible nitric oxide synthase switches off Th17 cell differentiation // Journal of Experimental Medicine. 2013. Vol. 210, no. 7. P. 1447–1462. doi: 10.1084/jem.20122494.Jianjun Y., Zhang R., Lu G., Shen Y., Peng L., Zhu C., Cui M., Wang W., Arnaboldi P., Tang M., Gupta M., Qi C.-F., Jayaraman P., Zhu H., Jiang B., Chen S.-h., He J. C., Ting A. T., Zhou M.-M., Kuchroo V. K., Morse 3rd H. C., Ozato K., Sikora A. G., Xiong H. T cell-derived inducible nitric oxide synthase switches off Th17 cell differentiation. Journal of Experimental Medicine. 2013; 210 (7): 1447–1462. doi: 10.1084/jem.20122494.Shehade H., Acolty V., Moser M., Oldenhove G. Cutting Edge: Hypoxia-Inducible Factor 1 Negatively Regulates Th1 Function // The Journal of Immunology. 2015. Vol. 195, no. 4. P. 1372–1376. doi: 10.4049/jimmunol.1402552.Shehade H., Acolty V., Moser M., Oldenhove G. Cutting Edge: Hypoxia-Inducible Factor 1 Negatively Regulates Th1 Function. Journal of Immunology. 2015; 195 (4): 1372–1376. doi: 10.4049/jimmunol.1402552.Touhidul S. M. I., Won J., Khan M., Mannie M. D., Singh I. Hypoxia-inducible factor-1 drives divergent immunomodulatory functions in the pathogenesis of autoimmune diseases // Immunology. 2021. Vol. 164, no. 1. P. 31–42. doi: 10.1111/imm.13335.Touhidul S. M. I., Won J., Khan M., Mannie M. D., Singh I. Hypoxia-inducible factor-1 drives divergent immunomodulatory functions in the pathogenesis of autoimmune diseases. Immunology. 2021; 164 (1): 31–42. doi: 10.1111/imm.13335.Yang X. O., Panopoulos A. D., Nurieva R., Chang S. H., Wang D., Watowich S. S., Dong C. STAT3 regulates cytokine-mediated generation of inflammatory helper T cells // Journal of Biological Chemistry. 2007. Vol. 282, no. 13. P. 9358–9363. doi: 10.1074/jbc.C600321200.Yang X. O., Panopoulos A. D., Nurieva R., Chang S. H., Wang D., Watowich S. S., Dong C. STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. Journal of Biological Chemistry. 2007; 282 (13): 9358–9363. doi: 10.1074/jbc.C600321200.Vuillefroy de Silly R., Ducimetiere L., Maroun C. Y., Dietrich P. Y., M. Derouazi M., and Walker P. R. Phenotypic switch of CD8+ T-cells reactivated under hypoxia toward IL-10 secreting, poorly proliferative effector cells // European Journal of Immunology. 2015. Vol. 45, no. 8. P. 2263–2275. doi: 10.1002/eji.201445284.Vuillefroy de Silly R., Ducimetiere L., Maroun C. Y., Dietrich P. Y., M. Derouazi M., Walker P. R. Phenotypic switch of CD8 + T cells reactivated under hypoxia toward IL-10 secreting, poorly proliferative effector cells. European Journal of Immunology. 2015; 45 (8): 2263–2275. doi: 10.1002/eji.201445284.Caldwell C. C., Kojima H., Lukashev D., Armstrong J., Farber M., Apasov S. G., Sitkovsky M. V. Differential effects of physiologically relevant hypoxic conditions on T-lymphocyte development and effector functions // Journal of Immunology. 2001. Vol. 167. P. 6140–6149.Caldwell C. C., Kojima H., Lukashev D., Armstrong J., Farber M., Apasov S. G., Sitkovsky M. V. Differential effects of physiologically relevant hypoxic conditions on T lymphocyte development and effector functions. Journal of Immunology. 2001; 167: 6140–6149.Thiel M., Caldwell C. C., Kreth S., Kuboki S., Chen P., Smith P., Ohta A., Lentsch A. B., Lukashev D., Sitkovsky M. V. Targeted deletion of HIF1alpha gene in T cells prevents their inhibition in hypoxic inflamed tissues and improves septic mice survival // Public Library of Science One. 2007. Vol. 2, iss. 9. e853. doi: 10.1371/journal.pone.0000853.Thiel M., Caldwell C. C., Kreth S., Kuboki S., Chen P., Smith P., Ohta A., Lentsch A. B., Lukashev D., Sitkovsky M. V. Targeted deletion of HIF1alpha gene in T cells prevents their inhibition in hypoxic inflamed tissues and improves septic mice survival. Public Library of Science One. 2007; 2 (9): e853. doi: 10.1371/journal.pone.0000853.Higashiyama M., Hokari R., Hozumi H., Kurihara C., Ueda T., Watanabe C., Tomita K., Nakamura M., Komoto S., Okada Y. et al. HIF-1 in T cells ameliorated dextran sodium sulfate-induced murine colitis // Journal of Leukocyte Biology. 2012. Vol. 91. P. 901–909.Higashiyama M., Hokari R., Hozumi H., Kurihara C., Ueda T., Watanabe C., Tomita K., Nakamura M., Komoto S., Okada Y. et al. HIF-1 in T cells ameliorated dextran sodium sulfate-induced murine colitis. Journal of Leukocyte Biology. 2012; 91: 901–909.Sumbayev V. V., Nicholas S. A., Streatfield C. A., Gibbs B. F. Involvement of hypoxia-inducible factor-1 HiF (1alpha) in IgE-mediated primary human basophil responses // European Journal of Immunology. 2009. Vol. 39, no. 12. P. 3511–3519. doi: 10.1002/eji.200939370.Sumbayev V. V., Nicholas S. A., Streatfield C. A., Gibbs B. F. Involvement of hypoxia-inducible factor-1 HiF (1alpha) in IgE-mediated primary human basophil responses. European Journal of Immunology. 2009; 39 (12): 3511– 3519. doi: 10.1002/eji.200939370.Yang M., Liu Y., Ren G., Shao Q., Gao W., Sun J., Wang H., Ji C., Li X., Zhang Y., Qu X. Increased expression of surface CD44 in hypoxia-DCs skews helper T cells toward a Th2 polarization // Scientific Reports. 2015. Vol. 1, no. 5. P. 13674. doi: 10.1038/srep13674.Yang M., Liu Y., Ren G., Shao Q., Gao W., Sun J., Wang H., Ji C., Li X., Zhang Y., Qu X. Increased expression of surface CD44 in hypoxia-DCs skews helper T cells toward a Th2 polarization. Scientific Reports. 2015; 1 (5): 13674. doi: 10.1038/srep13674.Niu Y., Wang J., Li Z., Yao K., Wang L., Song J. HIF1α deficiency in dendritic cells attenuates symptoms and inflammatory indicators of allergic rhinitis in a SIRT1-dependent manner // International Archives of Allergy and Immunology. 2020. Vol. 181, no. 8. P. 585–593. doi: 10.1159/000506862.Niu Y., Wang J., Li Z., Yao K., Wang L., Song J. HIF1α deficiency in dendritic cells attenuates symptoms and inflammatory indicators of allergic rhinitis in a SIRT1-dependent manner. International Archives of Allergy and Immunology. 2020; 181 (8): 585–593. doi: 10.1159/000506862.Kim S. R., Lee K. S., Park H. S., Park S. J., Min K. H., Moon H., Puri K. D., Lee Y. C. HIF-1α inhibition ameliorates an allergic airway disease via VEGF suppression in bronchial epithelium // European Journal of Immunology. 2010. Vol. 40, no. 10. P. 2858–2869. doi: 10.1002/eji.200939948.Kim S. R., Lee K. S., Park H. S., Park S. J., Min K. H., Moon H., Puri K. D., Lee Y. C. HIF-1α inhibition ameliorates an allergic airway disease via VEGF suppression in bronchial epithelium. European Journal of Immunology. 2010; 40 (10): 2858–2869. doi: 10.1002/eji.200939948.Mo J. H., Kim J. H., Lim D. J., Kim E. H. The role of hypoxia-inducible factor 1α in allergic rhinitis // American Journal of Rhinology and Allergy. 2014. Vol. 28, no. 2. P. e100–106. doi: 10.2500/ajra.2014.28.4025.Mo J. H., Kim J. H., Lim D. J., Kim E. H. The role of hypoxia-inducible factor 1α in allergic rhinitis. American Journal of Rhinology and Allergy. 2014; 28 (2): e100–106. doi: 10.2500/ajra.2014.28.4025.Zhou J., Zhang N., Zhang W., Lu C., Xu F. The YAP/HIF-1α/miR-182/EGR2 axis is implicated in asthma severity through the control of Th17 cell differentiation // Cell and Bioscience. 2021. Vol. 11, no. 1. P. 84. doi: 10.1186/s13578-021-00560-1.Zhou J., Zhang N., Zhang W., Lu C., Xu F. The YAP/HIF-1α/miR-182/EGR2 axis is implicated in asthma severity through the control of Th17 cell differentiation. Cell and Bioscience. 2021; 11 (1): 84. doi: 10.1186/s13578-021-00560-1.Crotty A. L. E., Akong-Moore K., Feldstein S., Johansson P., Nguyen A., McEachern E. K., Nicatia S., Cowburn A. S., Olson J., Cho J. Y., Isaacs H. Jr., Johnson R. S., Broide D. H., Nizet V. Myeloid cell HIF-1α regulates asthma airway resistance and eosinophil function // Journal of Molecular Medicine (Berlin). 2013. Vol. 91, no. 5. P. 637–644. doi: 10.1007/s00109-012-0986-9.Crotty A. L. E., Akong-Moore K., Feldstein S., Johansson P., Nguyen A., McEachern E. K., Nicatia S., Cowburn A. S., Olson J., Cho J. Y., Isaacs H. Jr., Johnson R. S., Broide D. H., Nizet V. Myeloid cell HIF-1α regulates asthma airway resistance and eosinophil function. Journal of Molecular Medicine (Berlin). 2013; 91 (5): 637–644. doi: 10.1007/s00109-012-0986-9.

The authors declare that there are no conflicts of interest present.