Previous studies revealed the expression of the

Previous studies revealed the expression of the CCR3 receptor in neurons and its neuroprotective function using mice lacking CCR3 expression (Wainwright et al., 2009). The regulation of CCR3 receptor expression in the microglia and astrocytes was shown in neurological disorders and has been demonstrated to be associated with microglial activation and regulation of the CNS (Flynn et al., 2003). The CCR3 receptor has been shown to play an important role in mediating neurological disorders. We showed for the first time that resveratrol has an immunosuppressive effect on the CCR3 receptor. In our present study, we found that the production of the CCR3 receptor was reduced by resveratrol treatment in both B6 and BTBR mice. In addition, we found that the levels of CCR3 mRNA expression was significantly altered after resveratrol treatment in the spleen and u73122 tissues. The CCR5 receptor antagonist improved the neurological outcomes such as reduced neurological deficit (Li et al., 2016). The CCR5 receptor is also expressed in human astrocytes and such sites might function in the recruitment of both astrocytes and leukocytes to specific regions of the brain during pathophysiological and physiological development (Andjelkovic et al., 1999). A previous study showed that CCR5 receptor inhibition is neuroprotective against ischemic stroke and injury (Reichel et al., 2006). We examined the effect of resveratrol on the production and expression levels of the CCR5 receptor and found it decreased in the BTBR mice. In line with these observations, we also showed that resveratrol treatment inhibited the mRNA expression in the spleen and brain tissues. Moreover, resveratrol decreased the CCR5 expression of BTBR mice, suggesting that it may be potentially useful in the treatment of autistic disorders. The inhibitory effects of resveratrol were also confirmed in the B6 mice, which exhibited a significant inhibition of the CCR5 receptor expression. These data suggest that the suppressive effect of resveratrol on CCR5 receptor production might be useful for controlling the chemokine receptor signaling in autistic diseases. Kivisakk et al. (2004) examined the expression level of CCR7 in the brain and found large numbers in the hippocampus. It has been also shown that CCR7 expression is upregulated in the CNS (Kivisakk et al., 2004). In the present study, we found for the first time that the expression of CCR7 significantly increased in the BTBR mice. Interestingly, we observed that resveratrol treatment significantly decreased the CD4+CCR7+ expression in the spleen cells. Furthermore, we found that the mRNA expression of CCR7 decreased in the spleen and brain tissues of BRBR mice following treatment with resveratrol. These observations indicate that the CCR7 receptor plays an important role in neuroinflammation. The CCR9 receptor has been implicated in neuroinflammatory diseases, and the frequency of circulating CD4+CCR9+ has been shown to increase in these conditions (Papadakis et al., 2001). Furthermore, the CCR9 receptor has been associated with other inflammatory disorders (Olaussen et al., 2007). We found that the CCR9 receptor production was higher in the BTBR control mice than it was in the B6 controls. Specifically, our data indicate that the CCR9 mRNA expression was higher in the brain and spleen tissues of the BTBR control mice than it was in the B6 mice. Therefore, we propose that the reduction of the expression of CCR9 mRNA and activity caused by resveratrol can contribute to the reduction of neuroinflammation. The chemokine CXC receptors play an important role in experimental autoimmune disorders (Bagaeva et al., 2006). The CXCR3 receptor is implicated in the pathogenesis of numerous neuroinflammatory diseases (Sørensen et al., 2002). The CXCR3 receptor expression has been reported in microglia and neurons and has been associated with the altered functionality of these cells (Biber et al., 2002). Cerebrospinal fluid investigations have shown significant enrichment of T cell-expressing CXCR3, which correlates with CNS pathology (Kivisäkk et al., 2002). The neuroinflammatory effect of the CXCR5 receptor has also been shown in the CNS (Bagaeva et al., 2006). Our data showed the BTBR control mice had increased CXCR3 and CXCR5 receptor expression, which was attenuated by resveratrol treatment. Hence, our study indicates the association of CXCR3 and CXCR5 receptors with autism.