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

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Science Immunology  25 Oct 2019:
Vol. 4, Issue 40, eaaw2707
DOI: 10.1126/sciimmunol.aaw2707

Pharmacological retraining for T cells

Regulatory T (Treg) cells expressing the Foxp3 transcription factor play a critical role in dampening overactive immune responses including autoimmune diseases. Akamatsu et al. screened a library of small molecules and identified a compound that promotes Treg differentiation on the basis of its ability to inhibit the cyclin-dependent kinases CDK8 and CDK19. The Treg-promoting activity of the CDK8/19 inhibitor did not require transforming growth factor–β (TGF-β) and reduced disease activity in mouse models of autoimmune diabetes and encephalomyelitis. These findings indicate that CDK8/19 inhibitors are a new class of immunomodulatory drugs capable of generating Treg cells with potential clinical applications in promoting tolerance and squelching autoimmunity.

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