Role of Gut Mucosal Immunity on Behavioral and Neuroinflammatory Profile in a Mouse Model of Autism – The Early-Life Immune-Activation Model

Monica Boirivant, Laura Ricceri, Roberta De Simone, Rosa Luisa Potenza
Istituto Superiore di Sanità in Rome, Italy

Inflammatory and immune changes are recognized as pivotal mechanisms in ASD, particularly the ones involving the microbiota-mucosal immune response development.

Few data are so far available in ASD mouse models concerning the primary contribution of mucosal immune dysfunction to behavioral and neuroinflammatory profiles as well as to dysbiosis.

This project aims to investigate the role of gut mucosal immunity on behavioral and neuroinflammatory profile in the early-life immune activation mouse (EIA), a model including both prenatal and postnatal immune challenges.

We plan to achieve our aim by the evaluation of the effect of selective blockade of gut-experienced lymphocyte traffic to intestinal lamina propria (by the administration of an antibody directed against the integrin alpha4 beta7, an integrin responsible for lymphocyte trafficking in the gut mucosa).

The effects of the treatment will be assessed on ASD-behavioral phenotype, on local (brain and gut-associated lymphoid tissue) and systemic (blood and spleen) immune-inflammatory changes, as well as on fecal microbiota composition.

Results will:

 a) clarify the mucosal contribution in ASD pathogenesis and

b) possibly provide specific biomarkers to be used in future studies to identify subsets of ASD patients for personalized therapeutic approaches.



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