Interleukin‑10 augments human endogenous retroviral E1B variant of cd5in aged T cells
10.1007/s44313-025-00080-8
- Author:
Bharat SINGH
1
;
Smita KUMARI
;
Amit Kumar KUREEL
;
Arunim SHAH
;
Shobhita KATIYAR 2
;
Chandra Prakash CHATURVEDI
;
Kulwant SINGH
;
Ambak KUMAR RAI
Author Information
1. Department of Biotechnology, Motilal Nehru National Institute of Technology Allahabad, Prayagraj‑211004 (U.P.), India
- Publication Type:RESEARCH
- From:Blood Research
2025;60():43-
- CountryRepublic of Korea
- Language:English
-
Abstract:
Purpose:Aging leads to immune dysfunction, including altered T-cell phenotypes such as the CD5 low state. This study investigated how the exon switch regulates CD5 expression in aging in an interleukin-10 (IL-10)-dominated environment and the involvement of CCAAT/enhancer-binding protein beta (CEBP-β) in this process.
Methods:The expression of messenger RNA (mRNA) was analyzed for E1A and E1B in T cells from young and older adults. The effect of IL-10 treatment on the exon switch was assessed by measuring the E1A and E1B mRNA expression in young T cells. MatInspector analysis identified CEBP-β binding sites upstream of E1A and E1B start sites.The effect of IL-10 on CEBP-β isoforms expression was assessed using western blot, and that on CEBP-β binding onto the E1A and E1B upstream was assessed using chromatin immunoprecipitation assays. The short hairpin RNA (shRNA) silencing of CEBP-β was performed to confirm its role in E1A/E1B expression.
Results:Older individuals showed increased E1B and decreased E1A mRNA expression. IL-10 treatment of young T cells persuaded a similar shift. IL-10 changed CEBP-β binding, reducing its association with the E1B upstream region while increasing its binding to E1A. IL-10 also upregulated the liver-enriched inhibitory protein of CEBP-β. shRNA silencing of CEBP-β reduced E1B expression.
Conclusion:IL-10-driven exon switching alters CD5 expression in aged T cells, increasing E1B and decreasing E1A through CEBP-β regulation. These findings reveal a novel mechanism underlying fundamental immune aging and suggest potential targets for immune modulation. These insights may have clinical implications in chronic inflammatory diseases, autoimmune disorders, and cancer therapies.
