The placental interleukin-6 signaling controls fetal brain development and behavior

Wei Li Wu, Elaine Y. Hsiao, Zihao Yan, Sarkis K. Mazmanian, Paul H. Patterson

Research output: Contribution to journalArticlepeer-review

100 Citations (Scopus)


Epidemiological studies show that maternal immune activation (MIA) during pregnancy is a risk factor for autism. However, mechanisms for how MIA affects brain development and behaviors in offspring remain poorly described. To determine whether placental interleukin-6 (IL-6) signaling is required for mediating MIA on the offspring, we generated mice with restricted deletion of the receptor for IL-6 (IL-6Rα) in placental trophoblasts (Cyp19-Cre+;Il6rafl/fl), and tested offspring of Cyp19-Cre+;Il6rafl/fl mothers for immunological, pathological and behavioral abnormalities following induction of MIA. We reveal that MIA results in acute inflammatory responses in the fetal brain. Lack of IL-6 signaling in trophoblasts effectively blocks MIA-induced inflammatory responses in the placenta and the fetal brain. Furthermore, behavioral abnormalities and cerebellar neuropathologies observed in MIA control offspring are prevented in Cyp19-Cre+;Il6rafl/fl offspring. Our results demonstrate that IL-6 activation in placenta is required for relaying inflammatory signals to the fetal brain and impacting behaviors and neuropathologies relevant to neurodevelopmental disease.

Original languageEnglish
Pages (from-to)11-23
Number of pages13
JournalBrain, Behavior, and Immunity
Publication statusPublished - 2017 May 1

All Science Journal Classification (ASJC) codes

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience


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