Genetic & environmental factors associated with Treg dysregulation & ASD

    Several genetic and environmental factors associated with ASD also play a role in Tregs development and stability. Genetic factors include genes typically linked to syndromic ASD (EHMT1, HDAC4, KMT2, CHD7), which are also involved in regulating epigenetic modifications essential for Tregs biology, such as those modulating the function & stability of Foxp3 proteins. Environmental factors also significantly contribute to Tregs dysregulation, particularly during gestation & early life. Maternal gut dysbiosis, infection, & pre-existing conditions can alter the developmental environment, specifically affecting T cell development within the thymus, & shifting the phenotype of cells that govern Tregs development toward an inflammatory profile. Furthermore, the chronic inflammation observed in ASD may destabilize the phenotype of existing Tregs, promoting the expression of transcription factors that drive differentiation toward inflammatory T cell types, such as TH17 cells. Consequently, the genetic and environmental factors associated with ASD & altered Tregs development can predispose individuals to pathological autoimmunity & immune-mediated comorbidities, such as gastrointestinal issues.

Reference

R.J. Moreno, R. Abu Amara, P. Ashwood, Toward a better understanding of T cell dysregulation in autism: An integrative review, Brain, Behavior, and Immunity, Volume 123, 2025, Pages 1147-1158, ISSN 0889-1591, https://doi.org/10.1016/j.bbi.2024.10.009.