@article{oai:oist.repo.nii.ac.jp:00002242, author = {Ban, Tatsuma and Kikuchi, Masako and Sato, Go R. and Manabe, Akio and Tagata, Noriko and Harita, Kayo and Nishiyama, Akira and Nishimura, Kenichi and Yoshimi, Ryusuke and Kirino, Yohei and Yanai, Hideyuki and Matsumoto, Yoshiko and Suzuki, Shuichi and Hihara, Hiroe and Ito, Masashi and Tsukahara, Kappei and Yoshimatsu, Kentaro and Yamamoto, Tadashi and Taniguchi, Tadatsugu and Nakajima, Hideaki and Ito, Shuichi and Tamura, Tomohiko}, journal = {Nature Communications}, month = {Jul}, note = {The transcription factor IRF5 has been implicated as a therapeutic target for the autoimmune disease systemic lupus erythematosus (SLE). However, IRF5 activation status during the disease course and the effects of IRF5 inhibition after disease onset are unclear. Here, we show that SLE patients in both the active and remission phase have aberrant activation of IRF5 and interferon-stimulated genes. Partial inhibition of IRF5 is superior to full inhibition of type I interferon signaling in suppressing disease in a mouse model of SLE, possibly due to the function of IRF5 in oxidative phosphorylation. We further demonstrate that inhibition of IRF5 via conditional Irf5 deletion and a newly developed small-molecule inhibitor of IRF5 after disease onset suppresses disease progression and is effective for maintenance of remission in mice. These results suggest that IRF5 inhibition might overcome the limitations of current SLE therapies, thus promoting drug discovery research on IRF5 inhibitors.}, title = {Genetic and chemical inhibition of IRF5 suppresses pre-existing mouse lupus-like disease}, volume = {12}, year = {2021} }