Abstract
Evidence suggests that immune dysregulation is associated with autism spectrum disorder (ASD). T cell immunoglobulin and mucin domain-3 (TIM-3) has a critical role in several inflammatory disorders; however, the role of TIM-3 signaling has not been demonstrated in ASD. In the present study, we assessed the role of TIM-3 signaling in children with ASD. We expected that increased numbers of TIM-3(+) cells could alter immune function in children with ASD. We revealed production of TIM-3 on CD3(+), CD4(+), CD8(+), CD11a(+),b(+), CD14(+), CD62P(+), and CXCR5(+) PBMCs in children with ASD and typically developing (TD) controls using immunofluorescent staining. We further demonstrated the production of IL-1 beta, IFN-gamma, IL-17A, and Foxp3 in TIM-3(+) PBMCs of TD controls and individuals with ASD. We also observed the mRNA expression levels of TIM-3, CD11a,b, CD14, IL-1 beta and IFN-gamma using RT-PCR. We further assessed the protein levels of TIM-3, IL-1 beta, CXCR5, and IFN-gamma using western blotting. The results showed that children with ASD had increased numbers of CD3(+)TIM-3(+), CD4(+)TIM-3(+), CD8(+)TIM-3(+), CD11a,b(+)TIM-3(+), CD14(+)TIM-3(+), CD62P(+)TIM-3(+) and CXCR5(+)TIM-3(+) cells compared with TD controls. Our results further showed that children with ASD had increased IL-1 beta+TIM-3(+), IFN-gamma+TIM-3(+), and IL-17(+)TIM-3(+), and decreased Foxp3(+)TIM-3(+) production compared with that in TD controls. Our results indicated that children with ASD significantly induced TIM-3, CD11a,b, CD14, CXCR5, IL-1 beta and IFN gamma mRNA and protein expression levels compared with TD controls. The results suggested that detection of TIM-3 signaling could contribute to the early diagnoses of ASD.