ISG15 protects human Tregs from interferon alpha-induced contraction in a cell-intrinsic fashion.

ABSTRACT:

Objectives

Type I interferons (IFNs) inhibit regulatory T-cell (Treg) expansion and activation, making them beneficial in antiviral responses, but detrimental in autoimmune diseases. Herein, we investigate the role of ISG15 in human Tregs in the context of refractoriness to type I IFN stimulation.

Methods

ISG15 expression and Treg dynamics were analysed in vitro and ex vivo from patients with chronic hepatitis C, with lupus and ISG15 deficiency.

Results

ISG15 is expressed at high levels in human Tregs, renders them refractory to the IFN-STAT1 signal, and protects them from IFN-driven contraction. In vitro, Tregs from healthy controls upregulate ISG15 upon activation to higher levels than conventional CD4 T cells, and ISG15-silenced Tregs are more

SUBMITTER: Pacella I 

PROVIDER: S-EPMC7758615 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature