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MINI REVIEW article

Front. Immunol.

Sec. T Cell Biology

This article is part of the Research TopicT Regulatory Cells: Mechanisms and Therapeutical AdvancesView all 11 articles

Regulatory T Cells in Hypoxic Environments

Provisionally accepted
Lourdes Gonzalez-RiveraLourdes Gonzalez-Rivera1,2Rodrigo Luna-GutierrezRodrigo Luna-Gutierrez3Stephanie CardenasStephanie Cardenas1Consuelo MerinoConsuelo Merino4Alex HandyAlex Handy1Ines PepperInes Pepper5Mercedes Natalia LopezMercedes Natalia Lopez1*
  • 1Núcleo Interdisciplinario de Farmacología e Inmunología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Independencia 1027, Universidad de Chile, Santiago, Chile
  • 2Departamento de inmunología, Hospital Clinico de la Universidad de Chile Jose Joaquin Aguirre, Santiago, Chile
  • 3Núcleo Interdisciplinario de Fisiología, Biofísica y Fisiopatología, Instituto de Ciencias Biomedicas (ICBM), Facultad de Medicina, Independencia 1027, Universidad de Chile, Santiago, Chile
  • 4Núcleo Interdisciplinario de Farmacología e Inmunología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Independencia 1027, Santiago, Chile, Universidad de Chile, Santiago, Chile
  • 5Universidad de Chile Facultad de Medicina, Santiago, Chile

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Oxygen availability is considered as an important determinant of immune regulation, yet its impact on regulatory T cells remains incompletely understood. In this review, we synthesize current evidence on how chronic and intermittent hypoxia influence the differentiation, stability and function of regulatory T cells across diverse physiological and pathological settings. We describe the main cellular pathways engaged during hypoxic adaptation, with emphasis on the role of hypoxia-inducible factors in shaping regulatory T cell metabolism and lineage integrity. We then evaluate findings from clinical contexts characterized by sustained or cyclical oxygen deprivation, including chronic lung disease, sleep-disordered breathing and severe viral infection. Across these conditions, hypoxia is associated with alterations in regulatory T cell phenotype and its suppressive function, although patterns vary according to microenvironment and disease stage. A clearer understanding of how distinct hypoxic patterns modulate regulatory T cell biology will be essential for identifying therapeutic strategies aimed at restoring immune balance in hypoxia-associated disease.

Keywords: COVID - 19, hypoxia, Hypoxia-inducible factor 1 (HIF-1), Obstructive, pulmonary disease, Regulatory, Regulatory T (Treg) cell, Sleep Apnea

Received: 27 Nov 2025; Accepted: 03 Feb 2026.

Copyright: © 2026 Gonzalez-Rivera, Luna-Gutierrez, Cardenas, Merino, Handy, Pepper and Lopez. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mercedes Natalia Lopez

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material