The Stat3 inhibitor, S31-201, downregulates lymphocyte activation markers, chemokine receptors, and inflammatory cytokines in the BTBR T+ Itpr3tf/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(tf)/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 S31-201, a selective Stat3 inhibitor, can be used to treat neuroinflammation disorders. Previously, we showed that S31-201 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 S31-201 in BTBR mice, and this was performed by investigating the effects of S31-201 treatment on lymphocyte activation markers (CD4(+) CD25(+) and CD4(+) CD69(+)), chemokine receptors (CD4(+) CCR6(+), CD4(+) CCR7(+), CD4(+) CXCR4(+), and CD4(+) CXCR5(+)), and proinflammatory cytokines (CD4(+) IL-6(+) and CD4(+) TNF-alpha(+)) in the spleen cells of BTBR and C57BL/6 (C57) mice. The mRNA and protein expression levels of CD69, CCR6, CCR7, CXCR4, CXCR5, IL-1 beta, IL-6, and TNF-alpha were examined in the brain tissues, and in BTBR mice, a significant decrease in CD25, CD69, CCR6, CCR7, CXCR4, CXCR5, IL-6, and TNF-alpha producing CD4(+) T cells was observed. The present findings suggest that treatment with S31-201 may be a therapeutic approach to improve immune abnormalities in a subgroup of autistic subjects.