La signalisation placentaire interleukine-6 contrôle le développement et le comportement du cerveau du foetus

Aperçu: G.M.

Des études épidémiologiques montrent que l'activation immunitaire maternelle (MIA) pendant la grossesse est un facteur de risque pour l'autisme. Cependant, les mécanismes de la MIA affectant le développement du cerveau et les comportements chez les descendants restent mal décrits.

Les résultats de l'étude démontrent que l'activation de l'IL-6 dans le placenta est nécessaire pour transmettre les signaux inflammatoires au cerveau fœtal et les comportements et les neuropathologies affectant le trouble neuro-dévelopemental. 

Brain Behav Immun. 2017 May;62:11-23. doi: 10.1016/j.bbi.2016.11.007. Epub 2016 Nov 9.

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

Wu WL¹, Hsiao EY², Yan Z³, Mazmanian SK⁴, Patterson PH⁵.

Author information

1

Division of Biology and Biological Engineering, California Institute of Technology, 1200 E. California Boulevard, Pasadena, CA 91125, USA. Electronic address: wlwu@caltech.edu

2

Division of Biology and Biological Engineering, California Institute of Technology, 1200 E. California Boulevard, Pasadena, CA 91125, USA; Department of Integrative Biology & Physiology, University of California, Los Angeles, 610 Charles E. Young Drive, Los Angeles, CA 90095, USA. Electronic address: ehsiao@ucla.edu.

3

Division of Biology and Biological Engineering, California Institute of Technology, 1200 E. California Boulevard, Pasadena, CA 91125, USA. Electronic address: Zihao_Yan@hms.harvard.edu.

4

Division of Biology and Biological Engineering, California Institute of Technology, 1200 E. California Boulevard, Pasadena, CA 91125, USA. Electronic address: sarkis@caltech.edu.

5

Division of Biology and Biological Engineering, California Institute of Technology, 1200 E. California Boulevard, Pasadena, CA 91125, USA. Electronic address: php@caltech.edu.

Abstract

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⁺;Il6ra^fl/fl), and tested offspring of Cyp19-Cre⁺;Il6ra^fl/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⁺;Il6ra^fl/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.

Copyright © 2016 Elsevier Inc. All rights reserved.

PMID: 27838335

DOI: 10.1016/j.bbi.2016.11.007