AccScience Publishing / JCBP / Online First / DOI: 10.36922/JCBP026140017
Submit to JCBP
Cite this article
2
Download
310
Views
Related Info Links
Google Scholar
More by Authors Links
Junhua Mei
Journal Browser
Volume | Year
Issue
Search
News and Announcements
View All
ORIGINAL RESEARCH ARTICLE

Analysis and exploration of peripheral T-cell subset characteristics and immune markers in patients with insomnia disorder

Xian Ding1† ,  Xinhua Song2† ,  Guang Wang3 ,  Zihan Gao4 ,  Minjie Lou4 ,  Yike Zhang4 ,  Meiyi Guo4 ,  Zhenghao Cao4 ,  Xin Liu2 ,  Junhua Mei2*
Show Less
1 Department of Neurology, School of Medicine, Jianghan University, Wuhan , Hubei
2 Department of Neurology, Wuhan No.1 Hospital, Wuhan, Hubei , China
3 Department of Neurology, School of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, Hubei , China
4 Department of Neurology, First Clinical College, Hubei University of Chinese Medicine, Wuhan, Hubei , China
†These authors contributed equally to this work.
JCBP, 026140017 https://doi.org/10.36922/JCBP026140017
Received: 31 March 2026 | Revised: 22 July 2026 | Accepted: 7 August 2026 | Published online: 26 August 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Download PDF
XML
Cite
Abstract

Chronic insomnia is closely associated with immune dysregulation; however, the immunometabolic characteristics of peripheral T-cell subsets and their relationship with sleep architecture remain largely unclear. This study investigated peripheral T-lymphocyte subsets and their immunometabolic characteristics in patients with chronic insomnia and identified immune indicators associated with sleep parameters. A total of 45 patients with chronic insomnia and 30 healthy controls were enrolled. Flow cytometry quantified T-cell subsets and two mitochondrial parameters: mitochondrial mass, reflecting mitochondrial content, and the percentage of cells with low mitochondrial membrane potential. A total of 37 patients underwent polysomnography. Multiple linear regression identified independent predictors after adjustment for age, sex, and anxiety/depression scores, while receiver operating characteristic analyses evaluated predictive performance. Compared with healthy controls, patients with insomnia showed imbalances in 21 of 30 immune indicators (p < 0.05), including increased frequencies of CD4+ CD45RA− CD62L− PD1+ effector memory T (Tem) cells, accompanied by increased mitochondrial mass and the percentage of cells with low mitochondrial membrane potential in this subset. Multivariate regression identified Tem cell percentage as an independent correlate of N1% (β = 0.184, p = 0.014) and Tem cell count as an independent correlate of sleep efficiency (β = −7.47, p = 0.007). Receiver operating characteristic analysis showed that Tem cell count predicted insomnia with an area under the curve of 0.858 (95% confidence interval: 0.761–0.955), a sensitivity of 95.6%, and a specificity of 66.7% at a cutoff of 18.015. Tem cell count may serve as an immunometabolic biomarker for insomnia assessment.

Keywords
Insomnia
Immunometabolism
Biomarker
Mitochondrial parameters
T cell subsets
Funding
This work was supported by the Hubei Province Natural Science Funding (Grant Number: 2025YFC109), the 2025 Municipal Natural Science Foundation (Grant Number: 2025020701020233), and the Hubei Provincial Administration of Traditional Chinese Medicine Research Project (Grant Number: ZY2025L039).
Conflict of interest
The authors declare no competing interests.
References
  1. Luo S, Yin J, Zhang J, et al. Genetically predicted leucine level mediates association between CD4/CD8br T lymphocytes and insomnia. Cell Mol Neurobiol. 2025;45(1). doi: 10.1007/s10571-025-01533-5
  2. Mithani S, Yun S, Leete JJ, et al. Whole blood transcriptome analysis using RNA sequencing in individuals with insomnia disorder and good sleepers: a pilot study. Sleep Med. 2021;80:1-8. doi: 10.1016/j.sleep.2021.01.013
  3. Tang N, Zeng Y, He G, Chen S. Interference between immune cells and insomnia: a bibliometric analysis from 2000 to 2023. Front Neurol. 2025;16. doi: 10.3389/fneur.2025.1486548
  4. Tan JX, Yu HR, Gu Y, Hong H. Distribution and function of human long-lasting T cells in aging and non-small cell lung cancer. Front Immunol. 2026;17. doi: 10.3389/fimmu.2026.1788541
  5. Li F, Feng Y, Yin Z, Wang Y. Mitochondrial metabolism in T-cell exhaustion. Int J Mol Sci. 2025;26(15):7400. doi: 10.3390/ijms26157400
  6. Zhang L, Dong J, Li Y, Jin J. Xanthine unveiled: bridging CD4+ T cell and stress-induced disorders through purine metabolism. Brain Behav Immun Integr. 2025;10:100113. doi: 10.1016/j.bbii.2025.100113
  7. Fan KQ, Li YY, Wang HL, et al. Stress-induced metabolic disorder in peripheral CD4+ T cells leads to anxiety-like behavior. Cell. 2019;179(4):864-879.e19. doi: 10.1016/j.cell.2019.10.001
  8. Chen Z, Lin Y, Wang B, Wang M. Mitochondrial remodeling by lithium drives CD4+ naïve T cell fate and immune homeostasis in bipolar disorder. Brain Behav Immun. 2026;137:106863. doi: 10.1016/j.bbi.2026.106863
  9. Chen Z, Wang B, Huang Y, Wang X, Li W, Wang M. Pathogenesis or a response to lithium? A novel perspective for mitochondrial mass fluctuation of naïve T cells in patients with bipolar disorder. J Affect Disord. 2024;355:86-94. doi: 10.1016/j.jad.2024.03.095
  10. Sakuishi K, Apetoh L, Sullivan JM, Blazar BR, Kuchroo VK, Anderson AC. Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J Exp Med. 2010;207(10):2187-2194. doi: 10.1084/jem.20100643
  11. Wu H, Prados M, Vaeth M. Metabolic regulation of T cell exhaustion. Immune Discov. 2025;1(1):10005. doi: 10.70322/immune.2025.10005
  12. Xu Y, Yuan W, Li K, Li P. Nutritional intervention alleviates T cell exhaustion and empowers anti-tumor immunity. Front Immunol. 2025;16. doi: 10.3389/fimmu.2025.1689317
  13. Maecker HT, McCoy JP, Nussenblatt R. Standardizing immunophenotyping for the Human Immunology Project. Nat Rev Immunol. 2012;12(3):191-200. doi: 10.1038/nri3158
  14. Cossarizza A, Chang HD, Radbruch A, et al. Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition). Eur J Immunol. 2019;49(10):1457-1973. doi: 10.1002/eji.201970107
  15. Steinert EM, Vasan K, Chandel NS. Mitochondrial metabolism regulation of T cell-mediated immunity. Annu Rev Immunol. 2021;39(1):395-416. doi: 10.1146/annurev-immunol-101819-082015
  16. Gage C, Koltun K, Bird M, et al. Systemic low-grade inflammation and associations with sleep disturbance in marine corps officer candidates during training. Int J Exerc Sci Conf Proc. 2024;9(12):95.
  17. Sauvet F, Chennaoui M. Sleep optimization to prevent sleep loss. J Sci Med Sport. 2017;20:S17. doi: 10.1016/j.jsams.2017.09.042
  18. Fernandes L. Efeitos da restrição de sono e exerc¨ªcio no metabolismo e imunidade [Effects of sleep restriction and physical exercise in metabolism and immunity]. Doctoral dissertation. Universidade Federal de São Paulo; 2016. [In Portuguese]. Accessed August 22, 2026. https://sucupira-legado.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=3724326
  19. Besedovsky L, Lange T, Haack M. The sleep-immune crosstalk in health and disease. Physiol Rev. 2019;99(3):1325-1380. doi: 10.1152/physrev.00010.2018
  20. Palagini L, Hertenstein E, Riemann D, Nissen C. Sleep, insomnia and mental health. J Sleep Res. 2022;31(4). doi: 10.1111/jsr.13628
  21. Sun L, Su Y, Jiao A, Wang X, Zhang B. T cells in health and disease. Sig Transduct Target Ther. 2023;8(1). doi: 10.1038/s41392-023-01471-y
  22. Goronzy JJ, Weyand CM. Mechanisms underlying T cell ageing. Nat Rev Immunol. 2019;19(9):573-583. doi: 10.1038/s41577-019-0180-1
  23. Han Y, Song Z, Li W, Ke P, Wu X. Analysis of the correlation between immune cell characteristics and insomnia: a Mendelian randomization study. J Neurophysiol. 2024;131(2):176-186. doi: 10.1152/jn.00429.2023
  24. Irwin MR. Sleep and inflammation: partners in sickness and in health. Nat Rev Immunol. 2019;19(11):702-715. doi: 10.1038/s41577-019-0190-z
  25. Irwin MR, Olmstead R, Carroll JE. Sleep disturbance, sleep duration, and inflammation: a systematic review and meta-analysis of cohort studies and experimental sleep deprivation. Biol Psychiatry. 2016;80(1):40-52. doi: 10.1016/j.biopsych.2015.05.014
  26. Vanek J, Prasko J, Genzor S, et al. Insomnia and emotion regulation. Neuro Endocrinol Lett. 2020;41(5):255-269.
  27. Yang MQ, Zhang SL, Sun L, et al. Targeting mitochondria: restoring the antitumor efficacy of exhausted T cells. Mol Cancer. 2024;23(1). doi: 10.1186/s12943-024-02175-9
  28. Sukumar M, Liu J, Mehta GU, et al. Mitochondrial membrane potential identifies cells with enhanced stemness for cellular therapy. Cell Metab. 2016;23(1):63-76. doi: 10.1016/j.cmet.2015.11.002
  29. van der Windt GJ, Everts B, Chang CH, et al. Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development. Immunity. 2012;36(1):68-78. doi: 10.1016/j.immuni.2011.12.007
  30. Wang H, Gao G, Ma H, et al. Reversal of remimazolam-mediated inhibition of Jurkat T cell activation by TGFBI depletion. Immune Discov. 2025;1(3):10009. doi: 10.70322/immune.2025.10009
Share
Back to top
Journal of Clinical and Basic Psychosomatics, Electronic ISSN: 2972-4414 Print ISSN: 3060-8562, Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept