Role of interleukin IL-17a in the differentiation and reactivity of astrocytes from individuals with autism

• Grant number: 24/10903-2
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: November 01, 2025
• End date: June 30, 2027
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Andréa Laurato Sertié
• Grantee: Bruno Yukio Yokota Moreno
• Host Institution: Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE). Sociedade Beneficente Israelita Brasileira Albert Einstein (SBIBAE). São Paulo , SP, Brazil

Abstract

Maternal immune activation (MIA) has been identified as an important environmental risk factor for Autism Spectrum Disorder (ASD). Animal models of MIA suggest that following infection and immune activation during pregnancy, maternal pro-inflammatory cytokines can cross the placenta and interfere with fetal brain development. Among these, interleukin 17a (IL-17a) appears to play an etiological role in the alterations of cerebral cytoarchitecture and ASD-like behavior in the offspring. The target cells of IL-17a in the developing brain are not fully known. It is speculated that one of the mechanisms by which IL-17a contributes to neurodevelopmental changes and ASD may be through its action on the differentiation and/or reactivity of astrocytes. However, the action of IL-17a on the astrocyte population, the molecular pathways through which it acts, and whether this response to IL-17a is deregulated in individuals with ASD are still not well understood. In this context, the main objectives of this research project are to verify whether IL-17a induces changes in the differentiation and reactivity of astrocytes derived from human induced pluripotent stem cells (hiPSCs) from individuals with ASD and control individuals, which molecular pathways are involved, and whether this response to IL-17a is different between the two groups. For this purpose, astrocytes cultured in monolayers and brain organoids derived from hiPSCs from individuals with ASD and controls will be used as experimental models, which will be treated with IL-17a or vehicle for different times, and then analyzed for: expression of astrocyte and reactive astrocyte markers, nuclear translocation of the transcription factor NF-kB, expression of pro-inflammatory molecules, morphology, proliferation, and reuptake of the neurotransmitter glutamate, and the intracellular pathways activated in each situation. (AU)