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Article

Physiological Oxygen Levels in the Microenvironment Program Ex Vivo-Generated Conventional Dendritic Cells Toward a Tolerogenic Phenotype

by
Antonia Peter
1,*,
Morgane Vermeulen
1,
Mats Van Delen
1,2,
Amber Dams
1,
Stefanie Peeters
1,3,
Hans De Reu
1,4,
Waleed F. A. Marei
5,6,
Zwi N. Berneman
1,3 and
Nathalie Cools
1,3,4
1
Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium
2
Health Department, Flemish Institute for Technological Research (VITO), 2400 Mol, Belgium
3
Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, 2650 Edegem, Belgium
4
Flow Cytometry and Sorting Core Facility (FACSUA), University of Antwerp, 2610 Antwerp, Belgium
5
Gamete Research Centre, Laboratory of Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, 2610 Antwerp, Belgium
6
Department of Theriogenology, Faculty of Veterinary Medicine, Cairo University, Giza 3725005, Egypt
*
Author to whom correspondence should be addressed.
Cells 2025, 14(10), 736; https://doi.org/10.3390/cells14100736
Submission received: 5 April 2025 / Revised: 13 May 2025 / Accepted: 14 May 2025 / Published: 18 May 2025
(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Immune Regulation)
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Abstract

Dendritic cells (DCs) are critical regulators of immune homeostasis, balancing tolerance and immunity through antigen presentation and T cell modulation. While the influence of hypoxia (<2% O2) on DC function in pathological settings is well-documented, the impact of physiological O2 levels remains underexplored. This study investigates the role of physioxia (4% O2) in programming mature DCs toward a tolerogenic phenotype compared to atmospheric conditions (21% O2) typically present in in vitro assays. DC cultures generated under 4% O2 exhibited a reduced monocyte-to-DC transformation rate, increased lactate production, a semi-mature surface marker profile, and increased surface expression of the tolerance-associated marker ILT4. T cell priming was altered only when atmospheric DCs were co-cultured under physioxia, suggesting an O2-dependent threshold for immunostimulatory capacity. These findings highlight the complexity of O2-dependent mechanisms in DC-T cell interactions, revealing a delicate balance between tolerance and immunogenicity. Our results underscore the need for physiologically relevant O2 conditions in DC research to better reflect in vivo behavior and inform immunotherapy design. Overall, this study advances understanding of how microenvironmental cues shape DC biology, with implications for immune tolerance, autoimmunity, and cancer immunotherapy.
Keywords: dendritic cells; microenvironment; oxygen; immunometabolism; dendritic-cell based immunotherapy dendritic cells; microenvironment; oxygen; immunometabolism; dendritic-cell based immunotherapy

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MDPI and ACS Style

Peter, A.; Vermeulen, M.; Van Delen, M.; Dams, A.; Peeters, S.; De Reu, H.; Marei, W.F.A.; Berneman, Z.N.; Cools, N. Physiological Oxygen Levels in the Microenvironment Program Ex Vivo-Generated Conventional Dendritic Cells Toward a Tolerogenic Phenotype. Cells 2025, 14, 736. https://doi.org/10.3390/cells14100736

AMA Style

Peter A, Vermeulen M, Van Delen M, Dams A, Peeters S, De Reu H, Marei WFA, Berneman ZN, Cools N. Physiological Oxygen Levels in the Microenvironment Program Ex Vivo-Generated Conventional Dendritic Cells Toward a Tolerogenic Phenotype. Cells. 2025; 14(10):736. https://doi.org/10.3390/cells14100736

Chicago/Turabian Style

Peter, Antonia, Morgane Vermeulen, Mats Van Delen, Amber Dams, Stefanie Peeters, Hans De Reu, Waleed F. A. Marei, Zwi N. Berneman, and Nathalie Cools. 2025. "Physiological Oxygen Levels in the Microenvironment Program Ex Vivo-Generated Conventional Dendritic Cells Toward a Tolerogenic Phenotype" Cells 14, no. 10: 736. https://doi.org/10.3390/cells14100736

APA Style

Peter, A., Vermeulen, M., Van Delen, M., Dams, A., Peeters, S., De Reu, H., Marei, W. F. A., Berneman, Z. N., & Cools, N. (2025). Physiological Oxygen Levels in the Microenvironment Program Ex Vivo-Generated Conventional Dendritic Cells Toward a Tolerogenic Phenotype. Cells, 14(10), 736. https://doi.org/10.3390/cells14100736

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