Nat Immunol: Multiple Sclerosis Has A New Treatment Option

Introduction: Multiple sclerosis (MS) is called "thousand-sided disease" and is an autoimmune disease characterized by the central nervous system's white myelin demyelinator lesionsThe most commonly affected areas of the disease are the white matter around the ventricle, the optic nerve, the spinal cord, the brain stem and the cerebellum, which is often shown in clinical practice as a multi-part dysfunction of the nervous system, prone to recurrenceMultiple sclerosis (MS) is known as a "thousand-sided disease""Thousand-sided disease" because the symptoms and progression of different patients can vary greatlyBut every multiple sclerosis patient has one thing in common: cells of the immune system in the patient's body migrate to the brain, and the cells of the immune system in the brain destroy myelin (the protective outer layer of nerve fibers), resulting in a short circuit that impedes the normal transmission of nerve signalsmany multiple drugs weaken immune memory
researchers are not yet able to determine which immune cells are involved in the peeling of myelin, and both auto-reactive T-cells and B cells identify myelin as a foreign body, transfer it to the brain and cause disease, a scientist at the Max Delbruck Molecular Medicine Center and senior author of the paper now published in Nature Immunology, said that so far, multiple drugs have been largely targeted at these T-cells and B-cells, both of which are part of acquired immunityMildner is currently conducting an externally funded study in The MDC's Asim Letz's laboratory as a DFG Heisenberg researcher, which focuses on cell differentiation and tumor development"By attacking the sexual immune system, multiple sclerosis drugs can have a negative impact on the body's immune memory, which in the long run makes patients more susceptible to infection," Mildner saidimprovedby reducing mononucleic cells in mice
so Mildner has been exploring a different strategy for years, hoping to find out the role of immune cells in the progression of multiple sclerosis, especially those innate immune cells, and whether immune cells represent a promising target structure for the treatment of multiple sclerosis patientsresearchers noted, "In early studies of multiple sclerosis in mice, we were able to see a significant reduction in disease symptoms in mice within a few days of the selective destruction of mononucleic cells in mice by antibodies." "The results came as a surprise to Mildner and his colleagues, and it was clear that it was not just T and B cells that caused tissue damage to multiple sclerosisMildner's study of monocytes is a special type of white blood cell that circulates rapidly in the blood before entering the tissue Once in the tissue, the mononucleosis are converted into effect cells (macrophages) and destroy the peripheral tissues of the central nervous system, where mononucleosis is misidentified during multiple sclerosis "This process can lead to inflammation and tissue damage to the brain," Mildner said the team discovered unknown mononucleosis types
the study, published in Nature Immunology, was conducted in collaboration with Professor Ido Amit of the Department of Immunology at the Weizmann Institute of Science in Israel Mildner and his team are also focusing on mononucleic cells, and the researchers say, "In recent years, we have realized that there are many types of these immune cells that may perform different functions." so we wanted to use single-cell sequencing to detect mononucleosis in more detail in mice and find out which monocytes subgroups are present in the brains of multiple sclerosis patients and cause tissue damage Mildner and his colleagues identified six monocytocell subgroups, four of which were not found at an early stage In Mildner's early studies, Mildner injected mice with antibodies to specific monocytocell surface proteins As expected, cell death reduces multiple sclerosis symptoms in mice in a short period of time "To our surprise, the antibodies don't destroy the mononucleosis of all of this surface protein in the brain, " says Mr Mildner not all mononucleosis can destroy protective myelin
Mildner said, "Only one specific mononucleosis (Cxcl10 plus cells) can be destroyed by antibodies, and it is clear that these cells are the main cause of multiple tissue damage in the brain." with the help of single-cell sequencing, Mildner and his team found that this cell type differs from other monocytes in two basic ways: first, Cxcl10 plus cells have a large number of signal protein receptors secreted by T cells that induce tissue damage characteristics of monocytes Second, these cells produce a large amount of leukocyl-1-beta, a substance that opens up the blood-brain barrier, making it easier for immune cells to transfer from the blood to the brain and worsening symptoms "Our study shows that T-cells are the initiators of multiple sclerosis, which are transmitted to the central nervous system in order to attract monocytes that cause major tissue damage," Mildner explained Mildner speculated that other mononuclear cell subgroups were also identified and may have been involved in the repair process (the body tried to reconstruct the damaged myelin) Given the findings of this study, Mildner believes that T-cells and B-cells may not be directly involved in the peeling of myelin It only indirectly promotes cxcl10 plus mononuclear cells to attack the protective layer of the axon many side effects may be avoidable
Mildner said that if so, many forms of future multiple sclerosis may be treated by specifically activating Cxcl10 plus mononucleosis, rather than t-cells and B cells of the immune system This protects the body's immune memory and avoids many side effects of current multiple sclerosis The team next plans to investigate the presence of Cxcl10-plus mononucleocytes on the periphery of the central nervous system, and if they exist on the periphery of the body, for example in lymph nodes, the lymph nodes are more easily targeted in the brain