Conversion of antigen-specific effector/memory T cells into Foxp3-expressing Treg cells by inhibition of CDK8/19

A promising way to harness hazardous immune responses, such as autoimmune disease and allergy, is to convert disease-mediating T cells into immuno-suppressive regulatory T (Treg) cells. Here we show that chemical inhibition of cyclin-dependent kinase (CDK) 8/19 is able to induce Foxp3, a key transcription factor controlling Treg cell function, in antigen-stimulated effector/memory as well as na?ve CD4+ and CD8+ T cells. The induction was dependent on STAT5 activation and not affected by inflammatory cytokines. In vivo administration of a newly developed CDK8/19 inhibitor along with antigen immunization generated functionally stable antigen-specific Foxp3+ Treg cells, which effectively suppressed skin contact hypersensitivity and autoimmune disease in animal models. This pharmacological conversion of antigen-specific effector/memory T cells into Foxp3+ Treg cells is instrumental for treating various immunological diseases.