Cell-cell communication by endocannabinoids during immune surveillance of the central nervous system

The immune system is designed to defend the organism from hazardous infection. The way by which cells of the immune system perform this function can be dangerous for the survival and function of the neuronal network in the brain. An attack of immune cells inside the brain includes the potential for severe neuronal damage or cell death and therefore impairment of CNS function. To avoid such undesirable action of the immune system, the CNS harbours an impressive arsenal of cellular and molecular mechanisms enabling strict control of immune reactions--the so-called "immune privilege". Under inflammatory and pathological conditions, loss of control of the CNS immune system results in the activation of neuronal damage cascades frequently associated with neurological disease. On the other hand, processes of neuroprotection and neurorepair after neuronal damage depend on a steady and tightly controlled immune surveillance. Accordingly, the immune system serves a highly specialized function in the CNS including negative feedback mechanisms that control immune reactions. Recent studies have revealed that endocannabinoids participate in one of the most important ones of the brain's negative feedback system. The CNS endocannabinoid system consists of cannabinoid receptors, their endogenous ligands and enzymes for the synthesis and degradation of endocannabinoids. It participates crucially in neuronal cell-cell-communication and signal transduction, e.g., by modulating synaptic input and protecting neurons from excitotoxic damage. Over the last decade, it has also become evident that endocannabinoids play an important role in the communication between immune cells, and in the interaction between nerve and immune system during CNS damage. Thus, therapeutic intervention in the CNS endocannabinoid system may help to restore the well-controlled and finely tuned balance of immune reactions in pathological conditions.