CDK8/CDK19 inhibition restores T-cell homeostasis in primary immune thrombocytopenia - PubMed

5 hours ago

CDK8/CDK19 inhibition promotes conversion of CD4+CD25- effector T cells (Teffs) into CD4+CD25+Foxp3+ regulatory T cells (Tregs).
The small-molecule inhibitor AS2863619 (AS) enhances STAT5 phosphorylation and Foxp3 induction, critical for Treg stability and function.
AS suppresses STAT3 phosphorylation, reducing Th17 polarization under IL-6-driven conditions.
Transcriptomic analysis shows AS broadly suppresses Teff differentiation while upregulating Treg signatures, mediated by STAT5, STAT3, and FOXP3.
AS induces metabolic reprogramming in T cells by suppressing glycolysis, supporting Treg conversion.
In a murine ITP model, CDK8/CDK19 inhibition increases Treg frequencies and improves thrombocytopenia in a STAT5-dependent manner.

Hasty Briefsbeta