International Meeting for Autism Research: Modeling An Autism Risk Factor in Mice Leads to Permanent Changes in the Immune System

Modeling An Autism Risk Factor in Mice Leads to Permanent Changes in the Immune System

Friday, May 21, 2010
Franklin Hall B Level 4 (Philadelphia Marriott Downtown)
1:00 PM
E. Hsiao , Biology, California Institute of Technology, Pasadena, CA
Background: Maternal infection can lead to the development of autistic endophenotypes in the offspring. Modeling this maternal infection risk factor in mice yields offspring with behavioral abnormalities and neuropathology resembling those characteristic of autistic individuals. A similar phenotype in the offspring can be obtained by activating the mother's immune system by injection of the double-stranded, synthetic RNA, poly(I:C). The cytokine IL-6 is a key mediator of the effects of maternal immune activation (MIA) on the fetus. Moreover, MIA activates downstream IL-6 signaling pathways in the placenta and in subpopulations of neurons in the fetal brain. In addition, IL-6 mRNA is induced in both of these tissues, which raises the possibility of a feed-forward mechanism that could lead to the permanent changes in immune status seen in the autistic brain and peripheral immune system. Studies have reported amplified immune responses in both peripheral tissues and the gastrointestinal tract of autistic subjects.

Objectives: We aim to study whether MIA during early fetal development alters later immune function in adult offspring.

Methods: Spleens and mesenteric lymph nodes were isolated from adult offspring of poly(I:C)- or saline-injected mothers. Tissues were mechanically and enzymatically disrupted to generate single cell suspensions. CD4+ T cells were isolated by magnetic bead separation (Miltenyi) and stimulated with PMA/ionomycin. IL-6 and IL-17 levels were measured from supernatants and normalized against number of cells.

Results: CD4+ T cells from spleen and mesenteric lymph nodes of adult poly(I:C) offspring display elevated levels of the pro-inflammatory cytokines IL-6 and IL-17 in response to stimulation in vitro.

Conclusions: MIA leads to significant changes in lymphocytes from the spleen and mesenteric lymph node of adult offspring. This observation indicates that MIA can cause permanent changes in immune status of the offspring.

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