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Significance PIP4Ks are druggable lipid kinases critical in cancer biology whose function in human immunity remains unknown. Here, we show that PIP4Ks specifically control the growth and activity of a subset of human immune cells called Tregs, isolated from the blood of healthy donors. Tregs function to exquisitely control the strength of the immune response. If the immune response is too strong, this can trigger autoimmune disease insurgence, while weak responses can lead to increased infections or enable tumor cell growth. Being able to selectively control Treg activity would impact the strength of immune responses and ultimately how we treat human diseases. Accordingly, we show that a drug-like inhibitor of PIP4K can be used to control Treg cell activity.

PIP4Ks impact on PI3K, FOXP3, and UHRF1 signaling and modulate human regulatory T cell proliferation and immunosuppressive activity