Increased placental T cell trafficking results in adverse neurobehavioral outcomes in offspring exposed to sub-chronic maternal inflammation

Christopher Novak, Ji Yeon Lee, Maide Ozen, Michael E. Tsimis, Lauren M. Kucirka, Michael W. McLane, Li Xie, Meredith Kelleher, Han Xie, Bei Jia, Jun Lei, Irina Burd

Research output: Contribution to journalArticle

Abstract

Interleukin-1 beta (IL-1β) is a cytokine mediator of perinatal brain injury. The effect of sub-chronic systemic IL-1β exposure in perinatal and offspring outcomes is unclear. The aim of this study was to examine the effects of maternal IL-1β exposure on pregnancy and offspring outcomes. At E15, CD1 dams were allocated to receive intraperitoneal injection of phosphate buffered saline or mouse recombinant IL-1β (1 mcg) for four consecutive days. We analyzed pup survival and neurobehavioral status. At E18, placental H&E staining and fetal brain Nissl staining was performed. Placental gene expression was analyzed by qPCR and T cell infiltration was analyzed by flow cytometry. Effects of inflammation on feto-placental blood flow were analyzed by Doppler ultrasonography. IL-1β decreased pup survival (P <.0001) and adversely affected offspring performance on neurodevelopmental tests (P <.05). Placentas of exposed dams exhibited significant thinning of maternal and fetal sides, and fetal brain exhibited cortical thinning. Placental qPCR analysis revealed significant upregulation of NFκB2 (P =.0021) and CXCL11 (P =.0401). While maternal IL-1β exposure did not affect feto-placental blood flow, placental flow cytometry showed an increase in placental infiltration of CD4+ T cells at 24 h post-injection (hpi, P <.0001) and CD8+ T cells at 72 hpi (P =.0217). Maternal sub-chronic, systemic inflammation with IL-1β decreased pup survival and played a key role in perinatal brain injury. The mechanisms behind these outcomes may involve immune system activation and alterations in placental T cell trafficking.

Original languageEnglish (US)
JournalBrain, Behavior, and Immunity
DOIs
Publication statusAccepted/In press - Jan 1 2018

    Fingerprint

Keywords

  • Interleukin-1β
  • Maternal inflammation
  • Perinatal brain injury
  • Placenta
  • T cells

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

Cite this