Spotlight on NJ Basic and Clinical Awards:

Nicholas Ponzio, Ph.D
University of Medicine and Dentistry of New Jersey
$449,997 for 3 years

Influence of the maternal immune response on the development of autism

Clinical and experimental evidence points to a role for the immune system during pregnancy in the development of autism spectrum disorders (ASD). Both T cells and cytokines (proteins which are produced by and regulate the behavior of immune cells) are implicated in various neurological disorders. Cytokines present in the maternal immune system can cross the placenta and enter fetal tissues, and this may affect fetal development. Preliminary results from the Ponzio laboratory have shown that the one such cytokine, interleukin-2 (IL-2) may affect fetal brain development, as the offspring of pregnant mice injected with IL-2 display abnormal behaviors. In the present study, these researchers will examine the role of maternal cytokines and immune cells as an environmental trigger for ASD.

Cytokines will be administered to pregnant mice by injection, and the effects on fetal brain development will be examined by behavioral testing of offspring for features selectively found in autism. IL-2 may act directly on the developing brain, or it may stimulate other components of the mother's immune system which in turn affects brain development. To determine which subsets of maternal immune cells and cytokines are stimulated by Il-2 treatment, the maternal immune system will be characterized by molecular and cell immunological techniques.

Correlating the activations of the immune system during pregnancy and the development of autistic-like characteristics in offspring will have clinical relevance for understanding the underlying causes of autism.

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Spotlight on NJ Environmental Factors and Autism Grants:

Nicholas Ponzio, Ph.D.
UMDNJ
$330,000 over 3 years

Influence of maternal cytokines during pregnancy on effector and regulatory T helper cells as etiological factors in autism

Despite the specific genes or environmental exposures which may contribute to ASD, one theme that emerges from clinical and experimental studies is inflammation and autoimmunity in individuals with ASD and their families. Such an immune response may be the consequence of genetic and environmental interactions leading to pathophysiology and symptomatology of the disorder. In order to better study the immune response, Dr. Ponzio and his colleagues propose to use well-documented experimental models of ASD to test the hypothesis that stimulation of the maternal immune system during pregnancy alters the normal proportions of newly discovered populations of lymphocytes known as T Helper 17 (TH17) cells and T regulatory (Treg) cells, the balance of which may be responsible for determining whether or not the observed neuroinflammation in ASD occurs. Activation of specific types of lymphocytes during an immune response causes secretion of proteins (known as cytokines) that can induce inflammation. If this occurs during pregnancy, these cytokines may cross the placenta, enter the fetus, and influence neural development and cause immunological outcomes and ASD-like behavior patters in the offspring. This experiment will examine different mechanisms by which cytokine secretions may mediate neural development, including whether or not they alter the placenta, whether they can enter fetal tissues, and if they promote differentiation of immune cells which alter the neuroinflammatory process.
What this means for people with autism: A better definition of the induction and function of Th17 and T regulatory (Treg) cells is critical in understanding the pathogenesis and regulation of inflammatory disorders and autoimmunity and will elucidate immunological mechanisms that may be triggered by environmental factors that promote the development and pathogenesis of ASD.

Click here for a full listing of Environmental Factors and Autism Grants