Mechanism of Immune Cell Entry into the Central Nervous System clarified for the first time in the world!
Mechanism of Immune Cell Entry into the Central Nervous System clarified
As part of Use-Inspired Fundamental Research under Grants-in-Aid from the Japan Science and Technology Agency , MURAKAMI Masaaki, Associate Professor at the Graduate School of Frontier Biosciences and HIRANO Toshio, President, et al, have shown that, at the molecular level, activation of the peripheral nervous system* 1 creates gates for the entry of immune cells into the brain and the spinal cord --the central nervous system (CNS)-- thereby making it possible for pathogenetic immune cells, if present in blood vessels in that region, to enter the CNS through the gates and cause disease.
Blood vessels in the CNS have been thought to form the blood-brain barrier (BBB)* 2 preventing viruses and large proteins from entering the brain and the spinal cord. However, the CNS has also been known to be affected by viruses and it is known that a variety of cancers and intractable diseases* 3 develop in the system. Therefore, it has theorized that there are gates of entry for immune cells through the BBB; however, the location of the gates and the process and mechanism have not been known.
The research group has revealed by using mice with a mouse model of multiple sclerosis* 4 that the gates for immune cell entry into the CNS are formed at a specific location and that such cells can more easily access the gates with activation of the local peripheral nervous system.
This research result has demonstrated a relationship between the nervous system and immune system at the molecular level, giving new possibilities for the development of prevention methods and medical treatments for cancer and other intractable diseases. Additionally, this result is expected to clarify the casual relationship between mental illness factors such as stress and a variety of diseases.
This research was conducted in cooperation with OOHIRA Yoshinobu, Professor at the Graduate School of Medicine of Osaka University and IWAKURA Yoichiro, Professor, The Institute of Medical Science of The University of Tokyo, et al. The research result was published on online breaking news of the American Science Magazine, Cell , on February 2, 2012 (US Eastern Time).
Notes
1. Nervous system
The nervous system of vertebrates consists of the central nervous system (CNS) and peripheral nervous system. The CNS contains the brain and the spinal cord and the peripheral nervous system contains the somatic nervous system and the autonomic nervous system. While the CNS is a cluster of nerve cells, the peripheral nervous system consists of nerve ganglia and nerves, playing a role of conveying nerve stimulation between the nervous system and body parts. The somatic nervous system regulating body movements and senses consists of the sensory nerves and motor nerves. The autonomic nervous system regulating organs and blood vessels consist of sympathetic nerves and parasympathetic nerves.
2. Blood-brain barrier (BBB)
The BBB is a mechanism of the CNS that separates the flow of blood from the brain extracellular fluid and thus from entering the CNS. Endothelial cells making up blood vessels of the central nervous system form a barrier to block large proteins and immune cells in blood vessels from passing through into the CNS.
3. Intractable diseases
Intractable diseases are diseases for which effective treatment is not available. Intractable diseases relating to the CNS include multiple sclerosis (MS), Alzheimer's, and Parkinson's disease.
4. Multiple sclerosis
The CNS has elongated strands called axons. Demyelination is caused by a loss of myelin around the axon of a neuron, the fatty protective sheath. Demyelination results in disruptions in the ability of nerves to communicate with one another, causing paralysis and numbness. The mechanism of demyelination has not been clarified; however, it is likely caused by an immune system abnormality.
