It is now well established that the immune system and the nervous system are connected bidirectionally ( 8, 9, 10 ). Although much remains to be investigated, several lines of evidence suggest that the sympathetic nervous system (SNS) provides a major pathway for neuroimmune interactions. Indeed, a role for catecholamines such as norepinephrine and epinephrine in SNS-mediated immunoregulation has been implicated in various conditions ( 11, 12, 13, 14, 15 ). Regarding the modulation of autoimmunity, it was previously demonstrated that depletion of SNS transmitters by chemical sympathectomy enhances the severity of EAE ( 11, 12 ). Because -adrenoceptor agonists protect against EAE ( 13 ) and catecholamines modulate several immunological functions critical to the pathogenesis of EAE ( 14 ), the enhancement of EAE by chemical sympathectomy has largely been attributed to the depletion of catecholamines. However, although neuropeptide Y (NPY) is also released from SNS terminals innervating lymphatic tissues ( 16, 17 ), no previous studies have explored the possibility that depletion of other SNS transmitters such as NPY may contribute to these findings.
Prior studies have revealed that the sympathetic nervous system regulates the clinical and pathological manifestations of experimental autoimmune encephalomyelitis (EAE), an autoimmune disease model mediated by Th1 T cells. Although the regulatory role of catecholamines has been indicated in the previous works, it remained possible that other sympathetic neurotransmitters like neuropeptide Y (NPY) may also be involved in the regulation of EAE.
In conclusion, this study demonstrates for the first time to our knowledge that NPY has an immunomodulatory activity that suppresses signs of EAE. Given that the levels of NPY in the CSF are reduced in patients with MS ( 34, 35 ), it is tempting to speculate that NPY may also play a critical role in preventing the development of MS. With the availability of novel and highly selective agonists and their ability to mimic the effects of NPY in a highly specific manner, we propose that targeting NPY receptors may be a promising new therapeutic approach to autoimmune disorders.
Department of Immunology, National Institute of Neuroscience, NCNP, Ogawahigashi, Kodaira, Tokyo, Japan; Department of Biochemistry, University of Leipzig, Leipzig, Germany; and Department of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany
