International Journal of Pediatric Otorhinolaryngology
Th17/Treg balance in children with obstructive sleep apnea syndrome and the relationship with allergic rhinitis
Introduction
OSA in children is usually caused by structural or functional abnormalities or by the obstruction of the upper airway. The most common cause of OSA in children is tonsil and/or adenoid hypertrophy. Adenoid tissue in the mucosa-associated lymphoid system of the upper respiratory tract is an important part of the Waldeyer ring. Inflammation in the nasopharynx and adjacent areas may cause repeated stimulation of the inflammatory response due to pathological adenoid hyperplasia [1]. Immune activation in the adenoids may occur following a variety of external stimuli, and the imbalance of local immune cells and an abnormal inflammatory response may lead to delayed healing, causing adenoidal hypotrophy. The adenoids’ local immune status is closely linked to the incidence of OSA. The synchronization of the inflammatory states of both the adenoids and the peripheral blood of children with OSA can help us understand the pathogenesis of OSA.
Sleep is closely related to the body's immune system. Ganz [2] believed that sleep is associated with immune function, and this relationship is partially based on the physiological basis of sleep, sleep architecture, the sleep-wake cycle, cytokines and the hypothalamic-pituitary axis. Many immune functions are dependent on circadian rhythms and regular sleep. Sleep disorders can cause changes in the number and function of immune cells, particularly T cells. Over the past decade, scholars have begun to focus research on subsets of T cells in OSA patients, including the Th1 and Th2 cell populations. Bollinger [3] found that there is a certain 24-h rhythm of the regulatory T cells (Treg) and that sleep deprivation seriously disrupts Treg cell function. Alert [4] studied patients with Th1-type active mode-based OSA, and Dyugovskaya [5] suggested that compared with wakefulness, early nocturnal sleep induced a shift in the Th1/Th2 cytokine balance towards increased Th1 activity; however, the Th1 shift was only moderate and was replaced by Th2 dominance during late sleep [6]. In recent years, Th17 and Treg T cell populations have also been discussed. Th17 cells are key effectors of the immune response. Th17 cells expressing retinoic acid-related orphan receptor γt (RORγt) play critical roles in the development of autoimmunity and allergic reactions through IL-17 production. Treg cells expressing the forkhead/winged helix transcription factor (Foxp3) orchestrate the overall immune response and play a role in immune tolerance through contact-dependent suppression or by regulating the activity of the effector T cells or releasing anti-inflammatory cytokines, such as interleukin-10 (IL-10) and transforming growth factor β (TGF-β1). Sade [7] found that the Th17/Treg ratio negatively correlates with the clinical score for OSA independent of age and gender. Jin Ye [8] found that the Th17/Treg ratio is elevated in patients with OSA and positively correlates with apnea–hypopnea index (AHI). Anderson [9] found that CD4 T cells are increased locally in the tonsils of children with OSA, whereas CD8 T cells are reduced, and that the Th17 cell population is affected. Although these results are varied and have yet to produce a unified conclusion, it is clear that T cell population imbalances, either Th1/Th2 or Th17/Treg imbalances, are observed in patients with OSA. This issue, however, requires further study and discussion.
Therefore, we have designed a research study of preschool-aged children (3–6 years) to measure the number of Th17 and Treg cells as well as the expression of related genes and cytokines in both the peripheral blood and adenoid tissue. Our aims are to investigate the significance of the Th17/Treg ratio in children with OSA, including the effect of changes in this ratio on the local and systemic inflammatory response, and to investigate how allergic rhinitis affects the Th17/Treg ratio in children with OSA.
Section snippets
Patient information
Children (ages 3 to 6 years) with OSA newly confirmed by overnight PSG were initially recruited into the OSA group. Children diagnosed with chronic tonsillitis who underwent surgical treatment and were excluded from a diagnosis of OSA by PSG were recruited into the control group. All patients were determined to be free of other cardiovascular, endocrine, urinary system, metabolic and neuromuscular diseases and disorders. The selected patients had no specific response to aspirin, bronchiectasis,
Subject characteristics
A total of 156 children were assessed, with 29 in group I (the control group without OSA and with levels I and II adenoid), 47 in group II (the OSA group with level III adenoids), 49 in group III (the OSA group with level IV adenoids), and 31 in group IV (OSHAS children with allergic rhinitis). The characteristics of the study population are shown in Table 2.
Preschool children aged 3–6 years were enrolled, and no statistically significant differences in age were found between the four groups (p >
Discussion
The newly discovered Th17 cells are a class of cells independent of the Th1 and Th2 T cell subsets. Th17 cells express RORγt and mainly secrete interleukin-17A (IL-17A). Th17 cells are an important class of effector T cells that regulate the body's fight against extracellular pathogens while also promoting the occurrence of autoimmune and inflammatory diseases. Th17 cells play an important role in the development of immunity, mainly by secreting IL-17. TNF-α and IL-6 also have a role in this
Conclusion
Our data confirm that the Th17/Treg ratio is increased in the peripheral blood and local adenoid tissue of OSA children. In cases of OSA of similar severity, changes in the Th17/Treg ratio are associated with adenoid size. The Th17/Treg ratio is also elevated in OSA children with allergic rhinitis to a greater extent than in children without AR. The Th17/Treg ratio may play a critical role in the pathogenesis of OSA in children, and AR may promote the process.
Conflict of interest statement
None of the participating institutions and authors have conflicts of interest regarding the study.
Acknowledgments
This study was supported by the Youth Research Fund of the Shanghai Municipal Health Bureau Item, China (no. 20124Y058), and by a project of the Shanghai Committee of Science and Technology, China (Grant No. 12411952407).
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