Cutting Edge: Inhibiting TBK1 by Compound II Ameliorates Autoimmune Disease in Mice.

ABSTRACT: TANK-binding kinase 1 (TBK1) is a serine/threonine protein kinase that plays a crucial role in innate immunity. Enhanced TBK1 function is associated with autoimmune diseases and cancer, implicating the potential benefit of therapeutically targeting TBK1. In this article, we examined a recently identified TBK1 inhibitor Compound II on treating autoimmune diseases. We found that Compound II is a potent and specific inhibitor of TBK1-mediated IFN response. Compound II inhibited polyinosinic-polycytidylic acid-induced immune activation in vitro and in vivo. Compound II treatment also ameliorated autoimmune disease phenotypes of Trex1(-/-) mice, increased mouse survival, and dampened the IFN gene signature in TREX1 mutant patient lymphoblasts. In addition, we found that TBK1 gene expression is

SUBMITTER: Hasan M 

PROVIDER: S-EPMC4635567 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature