# Interferon-stimulated Viperin impairs Treg function in autoimmune thrombocytopenia

## TL;DR

This study shows how a protein called Viperin, activated by interferon, disrupts the function of regulatory T cells in patients with immune thrombocytopenia, leading to autoimmune platelet destruction.

## Contribution

The study identifies the ELF1-Viperin pathway as a novel driver of Treg dysfunction in ITP.

## Key findings

- Tregs in ITP patients show increased interferon signaling and altered subset composition.
- Viperin overexpression impairs Treg function and promotes Th1 activation in conventional T cells.
- ELF1 activates Viperin transcription through epigenetic modifications.

## Abstract

Primary immune thrombocytopenia (ITP) is an autoimmune disorder driven by dysfunctional regulatory T cells (Tregs) that mediate platelet destruction. Here, we show that Tregs from ITP patients undergo a profound shift in subset composition and transcriptional states, with expansion of ANXA1high and IKZF2high populations and aberrant interferon signaling. Single-cell transcriptomic and functional analyses revealed that in normal controls, immature-like Tregs predominantly exhibit a FOXP3high/CCR6high phenotype, whereas in chronic ITP they adopt an ANXA1high state enriched for interferon-stimulated gene (ISG)high subclusters. Elevated ISG scores in chronic ITP Tregs mark a pathological transition, with RSAD2 (Viperin) emerging as a key regulator. Viperin overexpression impaired Treg suppressive function and promoted Th1-skewed activation in conventional T cells. Mechanistically, ELF1 directly binds the RSAD2 promoter and activates its transcription via increased H3K4Me3 deposition. These findings identify the ELF1-Viperin axis as the driver of Treg dysfunction in ITP and a potential target for therapeutic intervention.

The online version contains supplementary material available at 10.1186/s12964-025-02511-6.