A crosstalk between the immune system and obstructive sleep apnea
- 1Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University
- 2Departments of Pediatrics, Dentistry, Oral and Maxillofacial Surgery, and Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University
Abstract
Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstruction during sleep. Its hallmark pathophysiological features, intermittent hypoxia (IH) and sleep fragmentation (SF), trigger cellular and molecular responses that disrupt immune homeostasis. Recurrent hypoxia-reoxygenation promotes oxidative stress and activates hypoxia-inducible factor-1α (HIF-1α), nuclear factor-κB (NF-κB), and the NLRP3 inflammasome, contributing to sustained inflammatory signaling, endothelial dysfunction, and alterations in circulating and tissue-resident immune cells. This review integrates evidence from clinical and preclinical studies linking OSA to dysregulation of innate, adaptive, and humoral immunity and examines how these immune alterations contribute to OSA-associated systemic morbidity. Innate immune dysregulation in OSA is characterized by activation of neutrophils and monocytes/macrophages, increased oxidative stress, and elevated pro-inflammatory mediators, including IL-1β, IL-6, IL-8, TNF-α, CRP, and MCP-1. Altered expressions of ICAM-1 and VCAM-1 may further promote leukocyte recruitment and endothelial dysfunction, sustaining systemic inflammation and end-organ injury. Adaptive immune dysregulation includes alterations in CD4 ⁺ and CD8 ⁺ T-cell populations, Th1/Th17 polarization, disruption of the Th17/Treg balance, and impaired regulatory T-cell function. Emerging, although comparatively limited, evidence also implicates humoral immune dysregulation. Collectively, the interactions among IH, SF, oxidative stress, inflammation, and immune dysfunction support the concept that OSA is a systemic immune-modulating disorder rather than solely an upper airway disorder. Dysregulation of innate, adaptive, and humoral immunity may contribute to OSA-associated metabolic, cardiovascular, and neurocognitive complications. Defining these immune mechanisms may help explain OSA phenotypic heterogeneity and identify biomarkers of disease severity and therapeutic response. Furthermore, characterization of OSA-specific immune signatures may facilitate patient stratification and advance precision-medicine approaches based on individual inflammatory and immunological phenotypes.
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BibTeX
@article{ahmed2026crosstalk,
title = {{A crosstalk between the immune system and obstructive sleep apnea}},
author = {Sarfraz Ahmed and David Gozal and Alip Borthakur and Abdelnaby Khalyfa},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1963127},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1963127/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A crosstalk between the immune system and obstructive sleep apnea
AU - Sarfraz Ahmed
AU - David Gozal
AU - Alip Borthakur
AU - Abdelnaby Khalyfa
PY - 2026
DA - 2026/10/07
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1963127
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1963127/full
AB - Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstruction during sleep. Its hallmark pathophysiological features, intermittent hypoxia (IH) and sleep fragmentation (SF), trigger cellular and molecular responses that disrupt immune homeostasis. Recurrent hypoxia-reoxygenation promotes oxidative stress and activates hypoxia-inducible factor-1α (HIF-1α), nuclear factor-κB (NF-κB), and the NLRP3 inflammasome, contributing to sustained inflammatory signaling, endothelial dysfunction, and alterations in circulating and tissue-resident immune cells. This review integrates evidence from clinical and preclinical studies linking OSA to dysregulation of innate, adaptive, and humoral immunity and examines how these immune alterations contribute to OSA-associated systemic morbidity. Innate immune dysregulation in OSA is characterized by activation of neutrophils and monocytes/macrophages, increased oxidative stress, and elevated pro-inflammatory mediators, including IL-1β, IL-6, IL-8, TNF-α, CRP, and MCP-1. Altered expressions of ICAM-1 and VCAM-1 may further promote leukocyte recruitment and endothelial dysfunction, sustaining systemic inflammation and end-organ injury. Adaptive immune dysregulation includes alterations in CD4 ⁺ and CD8 ⁺ T-cell populations, Th1/Th17 polarization, disruption of the Th17/Treg balance, and impaired regulatory T-cell function. Emerging, although comparatively limited, evidence also implicates humoral immune dysregulation. Collectively, the interactions among IH, SF, oxidative stress, inflammation, and immune dysfunction support the concept that OSA is a systemic immune-modulating disorder rather than solely an upper airway disorder. Dysregulation of innate, adaptive, and humoral immunity may contribute to OSA-associated metabolic, cardiovascular, and neurocognitive complications. Defining these immune mechanisms may help explain OSA phenotypic heterogeneity and identify biomarkers of disease severity and therapeutic response. Furthermore, characterization of OSA-specific immune signatures may facilitate patient stratification and advance precision-medicine approaches based on individual inflammatory and immunological phenotypes.
SN - 1664-3224
ER -