# Interleukin-10 augments human endogenous retroviral E1B variant of cd5 in aged T cells

## TL;DR

This study shows how IL-10 affects CD5 expression in aged T cells through changes in gene regulation, offering new insights into immune aging and potential therapeutic targets.

## Contribution

The study identifies a novel IL-10-driven mechanism involving CEBP-β in regulating CD5 expression during immune aging.

## Key findings

- Older individuals show increased E1B and decreased E1A mRNA expression in T cells.
- IL-10 treatment of young T cells mimics the E1B/E1A shift seen in aging.
- IL-10 alters CEBP-β binding and upregulates its inhibitory isoform, affecting CD5 expression.

## Abstract

Aging leads to immune dysfunction, including altered T-cell phenotypes such as the CD5low 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.

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.

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.

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.

The online version contains supplementary material available at 10.1007/s44313-025-00080-8.