Prospect of ULK1 modulators in targeting regulatory T cells

Abstract

Regulatory T (Treg) cells play an instrumental role in coordinating immune homeostasis via potent inhibitory effects. Defects in Treg cells lead to autoimmunity, but an overwhelming proportion of Treg cells encourages cancer progression. Hence, targeting Treg cells has emerged as a promising approach for mitigating disease severity. Recent studies have revealed that kinases are a critical component for tuning the fate of Treg cells, but the entire network of Treg-modulating kinases is still unclear. Here, we propose that the autophagy-activating UNC-51-like kinase 1 (ULK1) is a candidate for Treg cell modulation. While accumulating evidence has highlighted the role of autophagy-related kinases in Treg cells, the ULK1-Treg cell axis is yet to be examined. In this review, we predicted the potential role of ULK1 in Treg cell modulation. Furthermore, we summarized current ULK1 activators and inhibitors that can be investigated as Treg-targeting strategies, which might have beneficial outcomes in autoimmunity and cancer.

Keywords: Autophagy; Regulatory T cells; Treg-targeting therapy; ULK1 modulator; UNC-51-like kinase 1.