DOI QR코드

DOI QR Code

Effector Memory CD8+ and CD4+ T Cell Immunity Associated with Metabolic Syndrome in Obese Children

  • Yang, Da-Hee (Graduate School, Jeju National University) ;
  • Lee, Hyunju (Department of Pediatrics, Jeju National University Hospital) ;
  • Lee, Naeun (Center for Integrative Rheumatoid Transcriptomics and Dynamics, The Catholic University of Korea) ;
  • Shin, Min Sun (Department of Internal Medicine, Yale University School of Medicine) ;
  • Kang, Insoo (Department of Internal Medicine, Yale University School of Medicine) ;
  • Kang, Ki-Soo (Department of Pediatrics, Jeju National University Hospital)
  • Received : 2021.01.17
  • Accepted : 2021.05.04
  • Published : 2021.07.15

Abstract

Purpose: We investigated the association of effector memory (EM) CD8+ T cell and CD4+ T cell immunity with metabolic syndrome (MS). Methods: Surface and intracellular staining of peripheral blood mononuclear cells was performed. Anti-interleukin-7 receptor-alpha (IL-7Rα) and CX3CR1 antibodies were used to stain the subsets of EM CD8+ T cells, while anti-interferon-gamma (IFN-γ), interleukin-17 (IL-17), and forkhead box P3 (FOXP3) antibodies were used for CD4+ T cell subsets. Results: Of the 47 obese children, 11 were female. Children with MS had significantly higher levels of serum insulin (34.8±13.8 vs. 16.4±6.3 µU/mL, p<0.001) and homeostasis model assessment of insulin resistance (8.9±4.1 vs. 3.9±1.5, p<0.001) than children without MS. Children with MS revealed significantly higher frequencies of IL-7Rαlow CD8+ T cells (60.1±19.1% vs. 48.4±11.5%, p=0.047) and IL-7RαlowCX3CR1+ CD8+ T cells (53.8±20.1% vs. 41.5±11.9%, p=0.036) than children without MS. As the serum triglyceride levels increased, the frequency of IL-7RαlowCX3CR1+ and IL-7RαhighCX3CR1- CD8+ T cells increased and decreased, respectively (r=0.335, p=0.014 and r=-0.350, p=0.010, respectively), in 47 children. However, no CD4+ T cell subset parameters were significantly different between children with and without MS. Conclusion: In obese children with MS, the changes in immunity due to changes in EM CD8+ T cells might be related to the morbidity of obesity.

Keywords

Acknowledgement

This research was supported by research grants from Jeju National University Hospital (JNUH-16-03) in 2016.

References

  1. WHO global health observatory data. Prevalence of obesity among children and adolescents [Internet]. Geneva: WHO; 2020 [cited 2020 Aug 4]. Available from: https://www.who.int/data/gho/data/themes/theme-details/GHO/body-mass-index-(bmi)
  2. Kang KS. Nutritional counseling for obese children with obesity-related metabolic abnormalities in Korea. Pediatr Gastroenterol Hepatol Nutr 2017;20:71-8. https://doi.org/10.5223/pghn.2017.20.2.71
  3. Friend A, Craig L, Turner S. The prevalence of metabolic syndrome in children: a systematic review of the literature. Metab Syndr Relat Disord 2013;11:71-80. https://doi.org/10.1089/met.2012.0122
  4. Wang HH, Lee DK, Liu M, Portincasa P, Wang DQ. Novel insights into the pathogenesis and management of the metabolic syndrome. Pediatr Gastroenterol Hepatol Nutr 2020;23:189-230. https://doi.org/10.5223/pghn.2020.23.3.189
  5. Zimmet P, Alberti KG, Kaufman F, Tajima N, Silink M, Arslanian S, et al. The metabolic syndrome in children and adolescents - an IDF consensus report. Pediatr Diabetes 2007;8:299-306. https://doi.org/10.1111/j.1399-5448.2007.00271.x
  6. Guzman-Flores JM, Ramirez-Emiliano J, Perez-Vazquez V, Lopez-Briones S. Th17 and regulatory T cells in patients with different time of progression of type 2 diabetes mellitus. Cent Eur J Immunol 2020;45:29-36. https://doi.org/10.5114/ceji.2020.94670
  7. Wang M, Chen F, Wang J, Zeng Z, Yang Q, Shao S. Th17 and Treg lymphocytes in obesity and Type 2 diabetic patients. Clin Immunol 2018;197:77-85. https://doi.org/10.1016/j.clim.2018.09.005
  8. Jung C, Lichtenauer M, Strodthoff D, Winkels H, Wernly B, Burger C, et al. Alterations in systemic levels of Th1, Th2, and Th17 cytokines in overweight adolescents and obese mice. Pediatr Diabetes 2017;18:714-21. https://doi.org/10.1111/pedi.12435
  9. Sell H, Habich C, Eckel J. Adaptive immunity in obesity and insulin resistance. Nat Rev Endocrinol 2012;8:709-16. https://doi.org/10.1038/nrendo.2012.114
  10. Odegaard JI, Ricardo-Gonzalez RR, Goforth MH, Morel CR, Subramanian V, Mukundan L, et al. Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature 2007;447:1116-20. https://doi.org/10.1038/nature05894
  11. Tiemessen MM, Jagger AL, Evans HG, van Herwijnen MJ, John S, Taams LS. CD4+CD25+Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages. Proc Natl Acad Sci U S A 2007;104:19446-51. https://doi.org/10.1073/pnas.0706832104
  12. Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, et al. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med 2009;15:914-20. https://doi.org/10.1038/nm.1964
  13. Sultan A, Strodthoff D, Robertson AK, Paulsson-Berne G, Fauconnier J, Parini P, et al. T cell-mediated inflammation in adipose tissue does not cause insulin resistance in hyperlipidemic mice. Circ Res 2009;104:961-8. https://doi.org/10.1161/CIRCRESAHA.108.190280
  14. Kim HR, Hong MS, Dan JM, Kang I. Altered IL-7Ralpha expression with aging and the potential implications of IL-7 therapy on CD8+ T-cell immune responses. Blood 2006;107:2855-62. https://doi.org/10.1182/blood-2005-09-3560
  15. Kim HR, Hwang KA, Kim KC, Kang I. Down-regulation of IL-7Ralpha expression in human T cells via DNA methylation. J Immunol 2007;178:5473-9. https://doi.org/10.4049/jimmunol.178.9.5473
  16. Shin MS, You S, Kang Y, Lee N, Yoo SA, Park K, et al. DNA methylation regulates the differential expression of CX3CR1 on human IL-7Rαlow and IL-7Rαhigh effector memory CD8+ T cells with distinct migratory capacities to the fractalkine. J Immunol 2015;195:2861-9. https://doi.org/10.4049/jimmunol.1500877
  17. Liu H, Jiang D. Fractalkine/CX3CR1 and atherosclerosis. Clin Chim Acta 2011;412:1180-6. https://doi.org/10.1016/j.cca.2011.03.036
  18. Oh MS, Kim S, Jang JH, Park JY, Kang HS, Lee MS, et al. Associations among the degree of nonalcoholic fatty liver disease, metabolic syndrome, degree of obesity in children, and parental obesity. Pediatr Gastroenterol Hepatol Nutr 2016;19:199-206. https://doi.org/10.5223/pghn.2016.19.3.199
  19. Oh MS, Kim S, Lee J, Lee MS, Kim YJ, Kang KS. Factors associated with advanced bone age in overweight and obese children. Pediatr Gastroenterol Hepatol Nutr 2020;23:89-97. https://doi.org/10.5223/pghn.2020.23.1.89
  20. Surendar J, Mohan V, Rao MM, Babu S, Aravindhan V. Increased levels of both Th1 and Th2 cytokines in subjects with metabolic syndrome (CURES-103). Diabetes Technol Ther 2011;13:477-82. https://doi.org/10.1089/dia.2010.0178