The Stat3 inhibitor, S31-201, downregulates lymphocyte activation markers, chemokine receptors, and inflammatory cytokines in the BTBR T+ Itpr3tf/J mouse model of autism
The Stat3 inhibitor, S31-201, downregulates lymphocyte activation markers, chemokine receptors, and inflammatory cytokines in the BTBR T+ Itpr3tf/J mouse model of autism
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DOI：
10.1016/j.brainresbull.2019.07.006
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发表时间：
2019-10-01
影响因子：
3.8
通讯作者：
Attia, Sabry M.
中科院分区：
文献类型：
--
作者：
Ahmad, Sheikh F.;Ansari, Mushtaq A.;Attia, Sabry M.
自闭症是一种发病率很高的复杂神经发育障碍。它的特点是缺乏沟通，缺乏社交技能，认知能力和刻板行为。在过去的几年里，自闭症在儿童中逐渐增加，但没有有效的治疗方法。BTBR T+ Itpr 3（tf）/J（BTBR）小鼠作为评估自闭症样行为的公认模型，因为它们显示出自闭症中显示的核心行为症状。先前的研究结果表明，S31-201是一种选择性Stat 3抑制剂，可用于治疗神经炎症疾病。之前，我们表明S31-201治疗对BTBR小鼠的自闭症样行为和Th 1/Th 17和调节性T细胞具有治疗作用。本研究的目的是进一步探讨S31-201在BTBR小鼠中的作用，这通过研究S31-201处理对淋巴细胞活化标志物（CD 4（+）CD 25（+）和CD 4（+）CD 69（+））、趋化因子受体（CD 4（+）CCR 6（+）、CD 4（+）CCR 7（+）、CD 4（+）CXCR 4（+）、和BTBR和C57 BL/6（C57）小鼠脾细胞中的CD 4（+）CXCR 5（+））和促炎细胞因子（CD 4（+）IL-6（+）和CD 4（+）TNF-alpha（+））。检测了脑组织中CD 69、CCR 6、CCR 7、CXCR 4、CXCR 5、IL-1 β、IL-6和TNF-α的mRNA和蛋白表达水平，在BTBR小鼠中，观察到产生CD 4（+）T细胞的CD 25、CD 69、CCR 6、CCR 7、CXCR 4、CXCR 5、IL-6和TNF-α显著减少。目前的研究结果表明，S31-201治疗可能是一种治疗方法，以改善免疫异常的自闭症患者的一个亚组。
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.