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Intermittent hypoxia induces Th17/Treg imbalance in a murine model of obstructive sleep apnea

Authors
 Do-Yang Park  ;  Chang-Hoon Kim  ;  Da-Young Park  ;  Hyun Jun Kim  ;  Hyung-Ju Cho 
Citation
 PLOS ONE, Vol.19(6) : e0305230, 2024-06 
Journal Title
PLOS ONE
Issue Date
2024-06
MeSH
Animals ; Cytokines / metabolism ; Disease Models, Animal* ; Hypoxia* / complications ; Hypoxia* / immunology ; Hypoxia-Inducible Factor 1, alpha Subunit / metabolism ; Interleukin-4 / metabolism ; Male ; Mice ; Mice, Inbred C57BL* ; Sleep Apnea, Obstructive* / immunology ; T-Lymphocytes, Regulatory* / immunology ; Th17 Cells* / immunology
Abstract
Obstructive sleep apnea (OSA) is characterized by cyclic normoxic and hypoxic conditions (intermittent hypoxia, IH) induced by the repeated closure of the upper-airway respiratory tract. As a pathomechanism of OSA, IH results in various comorbidities via chronic inflammation and related pathways. However, the role of other inflammatory cells, such as lymphocytes, has not been well-explored. This study aimed to examine the effects of IH on the distribution and balance of T cell subsets and other related cytokines, and mechanisms in the immune system. We modified OSA mouse model (male C57BL/6N male) using our customized chamber that controls specific sleep and oxygenic cycles. To induce hypoxia, the IH group was repeatedly exposed to 5% O2 and 21% O2 lasting for 120 s each for 7 h daily for 4 weeks. Mice were then subjected to a recovery period of 4 weeks, in which IH stimulation was ceased. T cells and related cytokines were analyzed using flow cytometry and immunohistochemistry. Compared with the control group, the IH group had significantly lower levels of CD4+CD25+Foxp3+ regulatory T cells but higher levels of Th 17, IL-4, HIF-1, and inflammatory cytokines. After the recovery period, these altered changes in the immune cells were recovered, and we found no significant difference in their levels between the control and recovery groups. This study revealed that the Th17/Treg ratio is increased by intermittent hypoxia, and this imbalance can explain immune-related diseases, including recently reported allergies, autoimmune, and even cancer diseases, arising from OSA.
Files in This Item:
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DOI
10.1371/journal.pone.0305230
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Chang Hoon(김창훈) ORCID logo https://orcid.org/0000-0003-1238-6396
Cho, Hyung Ju(조형주) ORCID logo https://orcid.org/0000-0002-2851-3225
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/202116
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