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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish
Article number14958
JournalInternational Journal Of Molecular Sciences
Volume23
Issue number23
DOIs
StatePublished - Dec 2022

Keywords

  • autoimmune hypophysitis
  • inhibitor
  • interleukin-1 receptor-associated kinase 1 (IRAK1)
  • pathogenesis

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