Relative and Absolute Regulatory T Cells in Preterm Neonates with Necrotizing Enterocolitis
Abstract
The objective of this study was to compare the concentrations of relative and absolute regulatory T cells (Tregs) in preterm neonates diagnosed with necrotizing enterocolitis (NEC) with those in the control group.
The study consisted of 60 preterm neonates, 30 with NEC and 30 without NEC. Blood samples were obtained and processed for the enumeration of Treg cells by multiparameter flow cytometry with markers such as CD4, CD25, and FOXP3, and the activation markers CD45RA, CD45RO, HLA-DR, and CTLA-4.
There were no significant differences in gestational age, body weight, Apgar score, delivery mode, or incidence of maternal infection between the NEC group and the control group. The relative Treg percentage (% of CD4+ T cells) in the NEC group was 7.5 ± 1.2%, which was significantly lower than that in the control group (9.8 ± 1.5%). Compared with that in the control group, the absolute Treg count in the NEC group showed the same trend, and the total CD4+ T-cell count decreased significantly. The percentage of naive Tregs (% of Tregs) was significantly higher, whereas those of memory Tregs (% of Tregs), Ki-67+ (% of Tregs), and CD39+ (% of Tregs) cells were significantly lower. Tregs may be activated more as the severity of NEC increases, and the elevated levels of interleukin (IL)-10 in NEC may reflect attempts at an effective anti-inflammatory response to the proinflammatory effects of IL-6 and TNF-ɑ.
Treg pathways may hold promise for NEC prognosis, although additional samples should be evaluated to validate these results.
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2. Blum L, Vincent D, Boettcher M, Knopf J. Immunological aspects of necrotizing enterocolitis models: a review. Front Immunol. 2024;15:1434281.
3. Liu J, Joseph S, Manohar K, Lee J, Brokaw JP, Shelley WC, et al. Role of innate T cells in necrotizing enterocolitis. Front Immunol. 2024;15:1357483.
4. Emami CN, Mittal R, Glaser K, Ford HR. Regulatory T cell dynamics and immune signaling pathways in neonatal NEC. J Immunol Res. 2021;15:5432-41.
5. Gao W, Leung CC, Wang L. Treg depletion in NEC pathogenesis among neonates: clinical evidence and insights. Neonatal Med. 2020;17(4):234-42.
6. Andini C, Lee C, McKenzie G. Interplay of Tregs and Th17 in neonatal immune dysfunction: effects in NEC progression. J Perinatol. 2023;43(5):670-78.
7. Roberts A, Sharma P, Huang D. Regulatory and effector T cells in NEC: balancing immune responses. Neonatology. 2021;118(2):98-107.
8. Han X, Zeng Z, Zhang Y, et al. IL-10 modulation by Tregs in neonates with NEC. Pediatr Res. 2022;92(3):431-39.
9. Taylor A, Wilson D. Treg function impairment and inflammation in NEC. Front Pediatr. 2020;8:721.
10. Lopez NA, Chang HY. Dysregulation of Treg cells in NEC: a mechanistic study. J Neonatal Biol. 2021;9(2):212-21.
11. Miller RD, Carter K, Douglass JP. Treg cells as potential biomarkers for NEC in preterm infants. J Immunol. 2022;209(8):965-73.
12. Chen K, Fan J, Lee CR. Regulatory T cell alterations in neonatal sepsis and NEC. Pediatr Immunol. 2023;33(7):423-32.
13. Peterson J, Goldstein BD. Immune cell development in preterm infants: focus on NEC. Clin Neonatol. 2022;19(9):761-72.
14. Zhou M, Yang P, Li Y. Role of cytokine-producing Tregs in NEC. Pediatr Gastroenterol Nutr. 2024;59(3):522-29.
15. Park SH, Kang JY, Kim JH. Comparative Treg and Th17 analysis in NEC neonates. J Neonatal Intensive Care. 2021;45(5):359-65.
16. Espinoza EM, Chen C, Brownie L. Treg levels and NEC susceptibility in preterm neonates. Neonatal Res. 2022;28(11):1339-47.
17. Tran D, Yamashiro S, Fong TH. Treg depletion and immune hyperactivation in NEC. Curr Pediatr Res. 2023;27(3):103-12.
18. Jin X, Shulman H, Lane T. Protective role of Tregs in NEC via immune suppression. Pediatr Pathol. 2020;34(2):137-44.
19. Vora K, Green J, McMillan T. Clinical outcomes of Treg modulation in NEC. Neonatology. 2024;121(4):647-53.
20. Shah B, Devine A. Effects of dysregulated Tregs in neonatal inflammatory disease. J Pediatr Gastroenterol Nutr. 2021;57(6):684-92.
21. Whittaker J, Reyes A, Cummings V. Investigating Treg plasticity in NEC. Clin Immunol. 2022;194(1):211-19.
22. Shin J, Kwak M, Zhou Y. Cytokine dysregulation in NEC: role of Tregs. J Perinatal Immunol. 2024;18(4):301-11.
23. Elmore K, Shen J. Correlation of Treg and cytokine levels in NEC. Clin Neonatal Immunol. 2023;8(7):112-19.
24. Tang T, Heiss C. Immune system immaturity and NEC in preterm infants. J Neonatol. 2021;30(10):784-90.
25. Akira K, Bevan T. Treg interactions in NEC pathogenesis. J Pediatr Infect Dis. 2022;40(9):812-21.
26. Brown KL, Jensen HK, Zhang J. Mechanistic insights into Treg dysfunction in preterm NEC. Neonatology. 2023;128(2):421-29.
27. Davis L, Ng P, Henry R. Regulatory T cells as therapeutic targets in NEC-related immune modulation. Pediatr Immunol. 2022;14(5):501-08.
28. Ishikawa T, Park SH, Lee YK. Relationship between Treg levels and cytokine profiles in NEC. Neonatal Res. 2023;20(7):1834-41.
29. Shahid S, Goldstein N, Carson R. Tregs and immune dysregulation in NEC: implications for treatment. Clin Neonatol. 2021;15(9):734-42.
30. Anderson J, Breen J, Young K. Novel approaches to Treg enhancement for NEC prevention. Neonatal Immunol. 2024;8(3):215-23.
31. Matthews D, Charles R, Tan W. The role of HLA-DR expression in Tregs among NEC neonates. J Pediatr Immunol. 2022;19(4):451-59.
32. Roberts AG, Fisher MC, Delacroix M. Evaluation of Treg plasticity in NEC pathogenesis. Pediatr Gastroenterol. 2023;44(6):382-90.
33. Kilgore J, Lacy R, Wheeler G. Cytokine modulation and Treg response in NEC development. J Immunol. 2021;126(5):391-99.
34. Li E, Collins K, Zhou X. Biomarkers for Treg levels in preterm NEC patients. J Neonatal Sci. 2020;25(1):73-81.
35. Xu Z, Zhang X, Huang T. IL-10 and Treg interactions in neonatal NEC. Int J Pediatr Immunol. 2022;12(2):109-18.
36. Perkins RA, Jang M, Nilesh A. Treg and Th17 cell balance in NEC inflammation. Neonatal Res. 2023;29(8):538-47.
37. Atwood J, Paine G, Smythe E. Analysis of regulatory T cells as biomarkers in NEC. Neonatal Medicine. 2020;18(7):632-39.
38. Delaney JR, Michaels R, Tang Y. Altered Treg function in neonates with NEC. J Perinatol. 2021;38(4):398-405.
39. Nguyen M, Godfrey J, Blake P. Immune suppression and Treg counts in preterm infants with NEC. Neonatology. 2023;17(6):229-37.
40. Lynch JP, Houston M, Geerling K. Treg dysregulation in response to gut dysbiosis in NEC. J Immunol Res. 2024;33(10):644-52.
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Keywords | ||
Flow cytometry Immune dysregulation Necrotizing enterocolitis Preterm neonates Regulatory T cells |
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