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.
González-Rivera et al. (Tue,) studied this question.