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Dysregulation of T cell immunoglobulin and mucin domain 3 (TIM-3) signaling in peripheral immune cells is associated with immune dysfunction in autistic children.

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-1β, IFN-γ, IL-17 A, 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-1β and IFN-γ using RT-PCR. We further assessed the protein levels of TIM-3, IL-1β, CXCR5, and IFN-γ 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-1β+TIM-3+, IFN-γ+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-1β and IFN-γ 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.

journal_name

Mol Immunol

journal_title

Molecular immunology

authors

Ahmad SF,Ansari MA,Nadeem A,Bakheet SA,Al-Ayadhi LY,Alotaibi MR,Alhoshani AR,Alshammari MA,Attia SM

doi

10.1016/j.molimm.2018.12.020

subject

Has Abstract

pub_date

2019-02-01 00:00:00

pages

77-86

eissn

0161-5890

issn

1872-9142

pii

S0161-5890(18)30784-3

journal_volume

106

pub_type

临床试验,杂志文章

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Dysregulation of T cell immunoglobulin and mucin domain 3 (TIM-3) signaling in peripheral immune cells is associated with immune dysfunction in autistic children.