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The Stat3 inhibitor, S3I-201, downregulates lymphocyte activation markers, chemokine receptors, and inflammatory cytokines in the BTBR T Itpr3/J mouse model of autism.

08:00 EDT 9th July 2019 | BioPortfolio

Summary of "The Stat3 inhibitor, S3I-201, downregulates lymphocyte activation markers, chemokine receptors, and inflammatory cytokines in the BTBR T Itpr3/J mouse model of autism."

Autism is a complex neurodevelopmental disorder with a high incidence rate. It is characterized by deficits in communication, a lack of social skills, cognitive inflexibility, and stereotypical behaviors. Autism has been gradually increasing in children over the past several years, without the existence of an effective treatment. BTBR T Itpr3/J (BTBR) mice serve as an accepted model to evaluate autistic-like behaviors as they display core behavioral symptoms displayed in autism. Previous findings showed that S3I-201, a selective Stat3 inhibitor, can be used to treat neuroinflammation disorders. Previously, we showed that S3I-201 treatment has therapeutic effects on autism-like behaviors, and Th1/Th17 and regulatory T cells in BTBR mice. The objective of the present study was to further explore the role of S3I-201 in BTBR mice, and this was performed by investigating the effects of S3I-201 treatment on lymphocyte activation markers (CD4CD25 and CD4CD69), chemokine receptors (CD4CCR6, CD4CCR7, CD4CXCR4, and CD4CXCR5), and proinflammatory cytokines (CD4IL-6 and CD4TNF-α) in the spleen cells of BTBR and C57BL/6 (C57) mice. The mRNA and protein expression levels of CD69, CCR6, CCR7, CXCR4, CXCR5, IL-1β, IL-6, and TNF-α were examined in the brain tissues, and in BTBR mice, a significant decrease in CD25, CD69, CCR6, CCR7, CXCR4, CXCR5, IL-6, and TNF-α producing CD4 T cells was observed. The present findings suggest that treatment with S3I-201 may be a therapeutic approach to improve immune abnormalities in a subgroup of autistic subjects.

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This article was published in the following journal.

Name: Brain research bulletin
ISSN: 1873-2747
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Medical and Biotech [MESH] Definitions

A chemokine that is a chemoattractant for MONOCYTES and may also cause cellular activation of specific functions related to host defense. It is produced by LEUKOCYTES of both monocyte and lymphocyte lineage and by FIBROBLASTS during tissue injury. It has specificity for CCR2 RECEPTORS.

A CC-type chemokine that is a chemoattractant for EOSINOPHILS; MONOCYTES; and LYMPHOCYTES. It is a potent and selective eosinophil chemotaxin that is stored in and released from PLATELETS and activated T-LYMPHOCYTES. Chemokine CCL5 is specific for CCR1 RECEPTORS; CCR3 RECEPTORS; and CCR5 RECEPTORS. The acronym RANTES refers to Regulated on Activation, Normal T Expressed and Secreted.

A CXC chemokine that is predominantly expressed in EPITHELIAL CELLS. It has specificity for the CXCR2 RECEPTORS and is involved in the recruitment and activation of NEUTROPHILS.

CXCR receptors that are expressed on the surface of a number of cell types, including T-LYMPHOCYTES; NK CELLS; DENDRITIC CELLS; and a subset of B-LYMPHOCYTES. The receptors are activated by CHEMOKINE CXCL9; CHEMOKINE CXCL10; and CHEMOKINE CXCL11.

A CC chemokine with specificity for CCR1 RECEPTORS and CCR5 RECEPTORS. It is a chemoattractant for NK CELLS; MONOCYTES; and a variety of other immune cells. This chemokine is encoded by multiple genes.

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