IL2RB affects Th1/Th2 and Th17 responses of peripheral blood mononuclear cells from septic patients

Main Article Content

Jiaqian Zhou
Ying Zhang
Qing Zhuang

Keywords

bioinformatics analysis, IL2RB, sepsis, Th1/Th2, Th17

Abstract

Background: Immune dysfunction is a common and serious complication of sepsis. This study finds key genes linked to immunity in sepsis.


Methods: The “Limma package” was used to analyze GSE154918 datasets for differentially expressed genes. The differentially expressed genes were then enriched for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and interleukin 2 receptor subunit Beta (IL2RB) protein coding gene was chosen for investigation. IL2RB expression in peripheral blood mononuclear cells (PBMC) was assessed by polymerase chain reaction. White blood cells of septic patients and healthy controls were collected from hospitals and linked with acute physiology and chronic health evaluation (APACHE) II, sequential organ failure assessment (SOFA), C-reactive protein (CRP), and procalcitonin (PCT) of septic patients using Pearson’s correlation analysis. PBMC cells were transfected with IL2RB, and the effect of transfection was observed on cellular interferon gamma (IFN-γ), interleukin (IL)-12, IL-4, IL-10, and IL-17A.


Results: A total of 686 differential genes, comprising 446 upregulated and 240 down regulated genes, were identified. The enrichment of KEGG pathway revealed that the majority of differential genes were enriched in the T helper (Th1)/Th2 cell and Th17 cell differentiation pathways. In patients with sepsis, correlation analysis revealed a negative correlation between IL2RB and APACHE II score, SOFA score, CRP, and PCT. IFN-γ and IL-12 levels were elevated in PBMC of septic patients after IL2RB transfection, but IL-4, IL-10, and IL-17A levels were lowered.


Conclusion: Sepsis-induced immunological dysfunction is improved by IL2RB, which also balances Th1/Th2 responses and prevents Th17 activation.

Abstract 130 | PDF Downloads 146 HTML Downloads 20 XML Downloads 5

References

1. Salomão R, Ferreira BL, Salomão MC, Santos SS, Azevedo LCP, Brunialti MKC. Sepsis: Evolving concepts and challenges. Braz J Med Biol Res. 2019;52(4):e8595. 10.1590/1414-431X20198595

2. Park GL, Park M, Min JK, Park YJ, Chung SW, Lee SJ. Anisomycin protects against sepsis by attenuating IκB kinase-dependent NF-κB activation and inflammatory gene expression. BMB Rep. 2021;54(11):545–50. 10.5483/BMBRep.2021.54.11.063

3. Kurt AN, Aygun AD, Godekmerdan A, Kurt A, Dogan Y, Yilmaz E. Serum IL-1 beta, IL-6, IL-8, and TNF-alpha levels in early diagnosis and management of neonatal sepsis. Mediators Inflamm. 2007;2007:31397. 10.1155/2007/31397

4. Liu Y, Wang X, Yu L. Th17, rather than Th1 cell proportion, is closely correlated with elevated disease severity, higher inflammation level, and worse prognosis in sepsis patients. J Clin Lab Anal. 2021;35(5):e23753. 10.1002/jcla.23753

5. Rimmelé T, Payen D, Cantaluppi V, Marshall J, Gomez H, Gomez A, et al. Immune cell phenotype and function in sepsis. Shock. 2016;45(3):282–91. 10.1097/SHK.0000000000000495

6. Rendon JL, Choudhry MA. Th17 cells: Critical mediators of host responses to burn injury and sepsis. J Leukoc Biol. 2012;92(3):529–38. 10.1189/jlb.0212083

7. Fu Q, Yu W, Fu S, Chen E, Zhang S, Liang TB. Screening and identification of key gene in sepsis development: Evidence from bioinformatics analysis. Medicine (Baltimore). 2020;99(27):e20759. 10.1097/MD.0000000000020759

8. Ning YL, Yang ZQ, Xian SX, Lin JZ, Lin XF, Chen WT. Bioinformatics analysis identifies Hub genes and molecular pathways involved in sepsis-induced myopathy. Med Sci Monit Int Med J Exp Clin Res. 2020;26:e919665. 10.12659/MSM.919665

9. Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021;47(11):1181–247. 10.1097/CCM.0000000000005337

10. Liang J, Wu W, Wang X, Wu W, Chen S, Jiang M. Analysis of sepsis markers and pathogenesis based on gene differential expression and protein interaction network. J Healthcare Eng. 2022;2022:6878495. 10.1155/2022/6878495

11. Lu J, Li Q, Wu Z, Zhong Z, Ji P, Li H, et al. Two gene set variation indexes as potential diagnostic tool for sepsis. Am J Transl Res. 2020;12(6):2749–59. eCollection 2020

12. Yang Y, Zhang Y, Li S, Zheng X, Wong MH, Leung KS, et al. A robust and generalizable immune-related signature for sepsis diagnostics. In: IEEE/ACM transactions on computational biology and bioinformatics. 2021; pp.

13. Li G, Wang Y, Cheng Y. IL2RB is a prognostic biomarker associated with immune infiltrates in pan-cancer. J Oncol. 2022;2022:2043880. 10.1155/2022/2043880

14. Suzuki H, Kündig TM, Furlonger C, Wakeham A, Timms E, Matsuyama T, et al. Deregulated T cell activation and autoimmunity in mice lacking interleukin-2 receptor beta. Science (New York). 1995;268(5216):1472–6. 10.1126/science.7770771

15. Lou W, Yan J, Wang W. Downregulation of miR-497-5p improves sepsis-induced acute lung injury by targeting IL2RB. BioMed Res Int. 2021;2021:6624702. 10.1155/2021/6624702

16. Zhang Q, Hu Y, Wei P, Shi L, Shi L, Li J, et al. Identification of hub genes for adult patients with sepsis via RNA sequencing. Sci Rep. 2022;12(1):5128. 10.1038/s41598-022-09175-z

17. Kim Y-J, Lee J-H, Lee S-W, Kim WY. Use of quick sequential organ failure assessment score-based sepsis clinical decision support system may be helpful to predict sepsis development. Signa Vitae. 2021;17(5):86–94. 10.22514/sv.2021.082

18. Brombacher F, Kastelein RA, Alber G. Novel IL-12 family members shed light on the orchestration of Th1 responses. Trends Immunol. 2003;24(4):207–12. 10.1016/s1471-4906(03)00067-x

19. Wei Y, Shan L, Qiao L, Liu R, Hu Z, Zhang W. Protective effects of Huang-Lian-Jie-Du-Tang against polymicrobial sepsis induced by cecal ligation and puncture in rats. Evidence Based Compl Alternat Med (eCAM). 2013;2013:909624. 10.1155/2013/909624

20. Ayala A, Deol ZK, Lehman DL, Herdon CD, Chaudry IH. Polymicrobial sepsis but not low-dose endotoxin infusion causes decreased splenocyte IL-2/IFN-gamma release while increasing IL-4/IL-10 production. J Surg Res. 1994;56(6):579–85. 10.1006/jsre.1994.1092

21. Iwasaka H, Noguchi T. Th1/Th2 balance in systemic inflammatory response syndrome (SIRS). Nihon Rinsho Jpn J Clin Med. 2004;62(12):2237–43. PMid: 15597790.

22. Yoon SJ, Kim SJ, Lee SM. Overexpression of HO-1 contributes to sepsis-induced immunosuppression by modulating the Th1/Th2 balance and regulatory T-cell function. J Infect Dis. 2017;215(10):1608–18. 10.1093/infdis/jix142