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Ban, Tatsuma; Kikuchi, Masako; Sato, Go R.; Manabe, Akio; Tagata, Noriko; Harita, Kayo; Nishiyama, Akira; Nishimura, Kenichi; Yoshimi, Ryusuke; Kirino, Yohei; Yanai, Hideyuki; Matsumoto, Yoshiko; Suzuki, Shuichi; Hihara, Hiroe; Ito, Masashi; Tsukahara, Kappei; Yoshimatsu, Kentaro; Yamamoto, Tadashi; Taniguchi, Tadatsugu; Nakajima, Hideaki; Ito, Shuichi; Tamura, Tomohiko
Nature communications, 07/2021, Letnik: 12, Številka: 1Journal Article
Abstract 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.
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Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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