{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T16:01:15Z","timestamp":1789488075137,"version":"build-2803163510"},"reference-count":304,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["25-15-00117"],"award-info":[{"award-number":["25-15-00117"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The connection between hypoxia and inflammation is well established at the local level, with HIF (hypoxia-inducible factor) playing a central role, which controls both the cellular response to oxygen deficiency and immune cell functioning. The literature contains extensive data regarding the roles of the transcription factors HIF, NF-\u03baB (a key regulator of inflammatory processes) and NRF2 (a master regulator of antioxidant defense), as well as the roles of oxidative stress level and mitochondrial functional features, in the response to oxygen deficiency and the development of inflammation. Meanwhile, at the systemic level, organisms differ according to hypoxia tolerance, which may determine differences in the functioning of these factors. Hypoxia-susceptible organisms are characterized by higher oxidative stress levels, HIF and glycolysis activity, and distinct mitochondrial functional features. These characteristics may underlie a baseline proinflammatory phenotype and are associated with innate immune cell function and the activation of trained immunity. For instance, under the systemic hypoxia, particularly during the ascent to high altitude, some individuals exhibit increased blood proinflammatory cytokine levels, which is usually connected with high-altitude disease development. A critical unsolved question is whether low hypoxia tolerance is a cause or a consequence of the systemic proinflammatory phenotype, or whether both are driven by an upstream factor, such as mitochondrial dysfunction. This review summarizes current literature data on the connection between initial organism hypoxia tolerance and the proinflammatory phenotype and examines the role of oxidative stress, mitochondria, and trained immunity in these processes.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1922856","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T14:32:16Z","timestamp":1789482736000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Low hypoxia tolerance as a determinant of the proinflammatory phenotype: a trained immunity perspective"],"prefix":"10.3389","volume":"17","author":[{"given":"Dzhuliia","family":"Dzhalilova","sequence":"first","affiliation":[{"name":"Petrovsky National Research Centre of Surgery","place":["Moscow, Russia"]},{"name":"Petrovsky Medical University","place":["Moscow, 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