The central nervous system (CNS) is isolated from the circulation, and protected behind barriers [the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB)]. As such, it has long been regarded as an immune privileged organ, and circulating leukocytes were assumed to be excluded from this tissue. Accordingly, it was accepted that any immune activity found in the brain is a response that promotes disease, and should be eliminated. In fact, almost every pathology of the brain and spinal cord, including acute injuries, as well as chronic neurodegenerative diseases such as Alzheimer’s disease, ALS, depression and even normal brain aging, are associated with local inflammation; thus, efforts were made to reduce inflammation in the brain through systemic administration of anti-inflammatory drugs. Nevertheless, in almost all CNS pathologies tested (other than inflammation-associated autoimmune diseases), these attempts to suppress systemic immunity as a way of mitigating brain inflammation were ineffective at best, or harmful.
Our pioneering studies have changed the understanding of the relationships between the brain and the immune system, by overturning the existing tenet, with clinical implications to age-related dementia, acute brain and spinal cord injury, Alzheimer’s disease and other neurodegenerative or neurodevelopmental diseases.
In our early studies, our group was the first to demonstrate that two types of immune cells, circulating blood macrophages, and T-cells recognizing brain components, are needed for healing the damaged central nervous system (CNS); these findings were conceptualized as the theory of “Protective autoimmunity”.
Beyond repair, we showed that the immune system is pivotal for life-long maintenance of the brain, enabling its proper function, as manifested by formation of new neurons, normal cognitive performance, and coping with mental stress (cognition/behavior and neurogenesis). According to our findings and formulated theory, immune cells that recognize self components of the CNS are pivotal for patrolling the healthy brain to identify any distressed situation and to resolve it before it develops into any disease, and to facilitate repair if pathology emerges. Thus, although the immune system is not part of the wired system of the brain, our work proposes that it helps maintain the environment of the brain in optimal condition, as required for its complex and delicate activity.