Idronoxil inhibition of TBK1 signalling

Purpose: Analysis of the transcriptional effects of Idronoxil (IDX) on primary bone marrow derived macrophages (BMDMs) from Trex1 mutant mice. Methods: Primary BMDMs from 3 different mice were treated overnight with Idronoxil at 1.25uM. RNA sequencing was performed with one NextSeq2000 P2 run using 19bp forward read and 101bp reverse reads. Conclusion: Idronoxil strongly decreased the basal TBK1 driven interferon gene signature in these cells. Overall design: Trex1-mutant mice have a single-base mutation in Trex1 leading to a premature stop codon (Q98X). Homozygous mutant mice have aberrant accumulation of cytoplasmic DNA, resulting in basal engagement of the cGAS-STING-TBK1 pathway (Ellyard J.I. and Vinuesa C.G., manuscript in preparation). Cells were treated overnight with 1.25uM Idronoxil prior to total RNA purification and RNA sequencing.