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Relevance of placental type I interferon beta regulation for pregnancy success

 Ja-Young Kwon  ;  Paulomi Aldo  ;  Yuan You  ;  Jiahui Ding  ;  Karen Racicot  ;  Xiaoyan Dong  ;  John Murphy  ;  Guy Glukshtad  ;  Michelle Silasi  ;  Jian Peng  ;  Li Wen  ;  Vikki M. Abrahams  ;  Roberto Romero  ;  Gil Mor 
 Cellular & Molecular Immunology, Vol.15(12) : 1010-1026, 2018 
Journal Title
 Cellular & Molecular Immunology 
Issue Date
ISGs ; Interferon beta ; TAM receptors ; cytokine ; immune regulation ; trophoblast ; type I interferon
Pregnancy is a unique immunologic and microbial condition that requires an adequate level of awareness to provide a fast and protective response against pathogens as well as to maintain a state of tolerance to paternal antigens. Dysregulation of inflammatory pathways in the placenta triggered by pathogens is one of the main factors responsible for pregnancy complications. Type I IFNs are key molecules modulating immune responses at the level of the placenta and are crucial for protection of the pregnancy via their antiviral and immune modulatory properties. In this study, we elucidate the mechanisms controlling the basal expression of IFNβ and its negative feedback. Using in vitro and in vivo animal models, we found that TLR signaling maintains basal IFNβ levels through the TLR4-MyD88-independent TBK/IRF3 signaling pathway. We describe the role of the TAM receptor Axl in the regulation of IFNβ function in human and mouse trophoblast cells. The absence of TAM receptors in vivo is associated with fetal demise due to dysregulation of IFNβ expression and its pro-apoptotic downstream effectors. Collectively, our data describe a feedback signaling pathway controlling the expression and function of IFNβ in the trophoblast that is essential for an effective response during viral and microbial infections.
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1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
Yonsei Authors
권자영(Kwon, Ja Young) ORCID logo https://orcid.org/0000-0003-3009-6325
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