Role of miRNAs in T-cell activation and Th17/Treg-cell imbalance in acquired aplastic anemia.
Int J Lab Hematol
; 46(3): 515-522, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38357712
ABSTRACT
BACKGROUND:
Altered T-cell repertoire with an aberrant T-cell activation and imbalance of the Th17/Treg cells has been reported in acquired aplastic anemia (aAA). miRNAs are well known to orchestrate T-cell activation and differentiation, however, their role in aAA is poorly characterized. The study aimed at identifying the profile of miRNAs likely to be involved in T-cell activation and the Th17/Treg-cell imbalance in aAA, to explore newer therapeutic targets.METHODS:
Five milliliters peripheral blood samples from 30 patients of aAA and 15 healthy controls were subjected to flow cytometry for evaluating Th17- and Treg-cell subsets. The differential expression of 7 selected miRNAs viz; hsa-miR-126-3p, miR-146b-5p, miR-155-5p, miR-16, miR-17, miR-326, and miR-181c was evaluated in the PB-MNCs. Expression analysis of the miRNAs was performed using qRT-PCR and fold change was calculated by 2-ΔΔCt method. The alterations in the target genes of deregulated miRNAs were assessed by qRT-PCR. The targets studied included various transcription factors, cytokines, and downstream proteins.RESULTS:
The absolute CD3+ lymphocytes were significantly elevated in the PB of aAA patients when compared with healthy controls (p < 0.0035), however, the CD4CD8 ratio was unperturbed. Th17 Treg-cell ratio was altered in aAA patients (9.1 vs. 3.7%, p value <0.05), which correlated positively with disease severity and the PNH positive aAA. Across all severities of aAA, altered expression of the 07 miRNAs was noted in comparison to controls; upregulation of miR-155 (FC-2.174, p-value-0.0001), miR-146 (FC-2.006, p-value-0.0001), and miR-17 (FC-3.1, p-value-0.0001), and downregulation of miR-126 (FC-0.329, p-value-0.0001), miR-181c (FC-0.317, p-value-0.0001), miR-16 (FC-0.348, p-value-0.0001), and miR-326 (FC-0.334, p-value-0.0001). Target study for these miRNAs revealed an increased expression of transcription factors responsible for Th1 and Th17 differentiation (T-bet, RORÏt, IL-17, IL-6, and IFN-Ï), T-cell activation (NFκB, MYC, and PIK3R2), downregulation of FOX-P3, and other regulatory downstream molecules like SHIP-1, ETS-1, IRAK-1, TRAF-6, and PTEN.CONCLUSION:
The study for the first time highlights the plausible role of different miRNAs in deregulating the Th17/Treg-cell imbalance in aAA, and comprehensively suggest the role of altered NF-kB and mTOR pathways in aAA. The axis may be actively explored for development of newer therapeutic targets in aAA.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ativação Linfocitária
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Linfócitos T Reguladores
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MicroRNAs
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Células Th17
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Anemia Aplástica
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Int J Lab Hematol
Ano de publicação:
2024
Tipo de documento:
Article