The Exposure to Lead (Pb) Exacerbates Immunological Abnormalities in BTBR T⁺ Itpr^3tf/J Mice through the Regulation of Signaling Pathways Relevant to T Cells

Autism spectrum disorder (ASD) is a common neurodevelopmental illness characterized by abnormal social interactions, communication difficulties, and repetitive and limited behaviors or interests. The BTBR T+ Itpr(3tf)/J (BTBR) mice have been used extensively to research the ASD-like phenotype. Lead (Pb) is a hazardous chemical linked to organ damage in the human body. It is regarded as one of the most common metal exposure sources and has been connected to the development of neurological abnormalities. We used flow cytometry to investigate the molecular mechanism behind the effect of Pb exposure on subsets of CD4(+) T cells in the spleen expressing IFN-gamma, T-bet, STAT1, STAT4, IL-9, IRF4, IL-22, AhR, IL-10, and Foxp3. Furthermore, using RT-PCR, we studied the effect of Pb on the expression of numerous genes in brain tissue, including IFN-gamma, T-bet, STAT1, STAT4, IL-9, IRF4, IL-22, AhR, IL-10, and Foxp3. Pb exposure increased the population of CD4(+)IFN-gamma(+), CD4(+)T-bet(+), CD4(+)STAT1(+), CD4(+)STAT4(+), CD4(+)IL-9(+), CD4(+)IRF4(+), CD4(+)IL-22(+), and CD4(+)AhR(+) cells in BTBR mice. In contrast, CD4(+)IL-10(+) and CD4(+)Foxp3(+) cells were downregulated in the spleen cells of Pb-exposed BTBR mice compared to those treated with vehicle. Furthermore, Pb exposure led to a significant increase in IFN-gamma, T-bet, STAT1, STAT4, IL-9, IRF4, IL-22, and AhR mRNA expression in BTBR mice. In contrast, IL-10 and Foxp3 mRNA expression was significantly lower in those treated with the vehicle. Our data suggest that Pb exposure exacerbates immunological dysfunctions associated with ASD. These data imply that Pb exposure may increase the risk of ASD.