Inhibition of IRAK1 Is an Effective Therapy for Autoimmune Hypophysitis in Mice

Hsiao Chen Huang, Yun Ti Chen, Han Huei Lin, Zhi Qin Li, Jinn Moon Yang*, Shey Cherng Tzou*


研究成果: Article同行評審

1 引文 斯高帕斯(Scopus)


Autoimmune hypophysitis (AH) is an autoimmune disease of the pituitary for which the pathogenesis is incompletely known. AH is often treated with corticosteroids; however, steroids may lead to considerable side effects. Using a mouse model of AH (experimental autoimmune hypophysitis, EAH), we show that interleukin-1 receptor-associated kinase 1 (IRAK1) is upregulated in the pituitaries of mice that developed EAH. We identified rosoxacin as a specific inhibitor for IRAK1 and found it could treat EAH. Rosoxacin treatment at an early stage (day 0–13) slightly reduced disease severity, whereas treatment at a later stage (day 14–27) significantly suppressed EAH. Further investigation indicated rosoxacin reduced production of autoantigen-specific antibodies. Rosoxacin downregulated production of cytokines and chemokines that may dampen T cell differentiation or recruitment to the pituitary. Finally, rosoxacin downregulated class II major histocompatibility complex expression on antigen-presenting cells that may lead to impaired activation of autoantigen-specific T cells. These data suggest that IRAK1 may play a pathogenic role in AH and that rosoxacin may be an effective drug for AH and other inflammatory diseases involving IRAK1 dysregulation.

期刊International Journal Of Molecular Sciences
出版狀態Published - 12月 2022


深入研究「Inhibition of IRAK1 Is an Effective Therapy for Autoimmune Hypophysitis in Mice」主題。共同形成了獨特的指紋。