Supersulphides suppress type-I and type-II interferon responses by blocking JAK/STAT signalling in macrophages.

This article focuses on the inhibitory effects of supersulphide donors on interferon (IFN) signalling in macrophages, highlighting their potential as therapeutic agents for autoimmune diseases characterized by dysregulated IFN activity. Supersulphide donors such as N-acetyl-L-cysteine tetrasulphide (NAC-S2) and thioglucose tetrasulphide (TGS4) were shown to suppress phosphorylation of Janus kinases (JAKs) and signal transducer and activator of transcription 1 (STAT1) in response to both type-I (IFN-α/β) and type-II (IFN-γ) IFNs, thereby inhibiting downstream inflammatory mediators like tumor necrosis factor-alpha (TNF-α) and inducible nitric oxide synthase (iNOS). The study distinguishes these effects from those of hydrogen sulphide (H2S) donors, which did not inhibit IFN signalling under the tested conditions. These findings suggest that intracellular elevation of supersulphides interferes with JAK/STAT signalling pathways, providing a molecular basis for developing supersulphide-based treatments targeting autoimmune disorders involving IFN overactivation.