Cutting edge: Inhibiting TBK1 by compound II ameliorates autoimmune disease in mice

Maroof Hasan, Nicole Dobbs, Shaheen Khan, Michael A. White, Edward K. Wakeland, Quan Zhen Li, Nan Yan

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


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 elevated in systemic lupus erythematosus patient cells, and systemic lupus erythematosus cells with high IFN signature responded well to Compound II treatment. Together, our findings provided critical experimental evidence for inhibiting TBK1 with Compound II as an effective treatment for TREX1-associated autoimmune diseases and potentially other interferonopathies.

Original languageEnglish (US)
Pages (from-to)4573-4577
Number of pages5
JournalJournal of Immunology
Issue number10
StatePublished - Nov 15 2015

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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