Major scientific discovery of Professor Liu Qiang's team from the General Hospital of Tianjin Medical University: bone marrow immunity will become a new target for multiple sclerosis treatment. Research achievements were published in the top issue of the scientific journal Cell
Tianjin Medical University published a thesis in Cell as the first unit
Multiple sclerosis (MS) is the most important cause of autoimmune demyelinating disease of central nervous system and disability of young adults in the world. The autoimmune reaction led by T lymphocytes attacks the myelin sheath, involving the optic nerve, spinal cord, brain stem, white matter around the ventricles and other parts, resulting in vision abnormalities, limb movement disorders, ataxia and other clinical symptoms. The core mechanism of MS is the loss of autoimmunity tolerance of T lymphocytes. However, its trigger factors, location, and how to maintain self-reactivity and drive the mechanism of disease progression are still unclear. Therefore, there is no cure for MS at present, and the drug efficacy to control the disease progression is also very limited.
In the past, the research on the pathogenesis of multiple sclerosis was limited to autoreactive T cells from peripheral blood and cerebrospinal fluid. As the main hematopoietic organ of adults, bone marrow is also the central immune organ of adult T cell development, which plays a key role in initiating and maintaining the immune response of the body. However, it is still unknown what role bone marrow plays in the origin and evolution of autoimmune reaction, and what impact it has on the progression of MS disease.
On June 15, 2022, the research team of Professor Liu Qiang, Department of Neurology, General Hospital of Tianjin Medical University, published a thesis entitled "Bone marrow hematopoiesis drives multiple sclerosis progression" in Cell. Using single cell sequencing, lineage analysis and flow cytometry, the research group found that the hematopoietic stem cells (HSCs) in the upstream of the bone marrow hematopoietic system of MS patients were activated, and then biased towards the myeloid system, resulting in significant increase of monocytes and neutrophils in the downstream. In order to evaluate the effect of myeloid hyperplasia on autoreactive T cells, the research team used TCR sequencing to find that the number and diversity of T cell clones in the bone marrow of MS patients increased significantly.
In order to explore the cause of myeloid hyperplasia in bone marrow of MS patients, the research team found that a large number of nerve antigen specific T cells were homing into bone marrow under the guidance of chemokine CXCL12 through proteomics. Nano-string RNA sequencing showed that the neural antigen specific T cells highly expressed CCL5 after reaching the bone marrow, causing myeloid hyperplasia. In order to analyze the effect of abnormal myeloid hyperplasia on the central nervous system, the research group used lineage tracing technology to describe the fate map of bone marrow newborn cells in MS mouse model, and found that the bone marrow newborn myeloid cells expanded neural antigen specific T cells in bone marrow and brain, accelerating demyelination injury in brain and spinal cord. These findings suggest that abnormal myeloid hyperplasia in bone marrow drives the progression of multiple sclerosis.
On the basis of these new findings, the research group put forward a new theory of "returning to the steady state of the immune system and reducing the inflammatory damage of the nervous system by rebalancing the bone marrow hematopoietic system". Recently, the research group hosted a multicenter clinical study based on the new therapy of "bone marrow immune regulation" theory (NIH clinical trial registration number: NCT05154734, NCT05369351), and practiced the medical research paradigm of "clinical issue - basic research - clinical transformation", which may open up a new way to treat MS and related neuroimmune diseases such as optic myelitis.
Liu Qiang's research group systematically studied the pathological role of the immune system in different types of brain diseases, such as cerebral apoplexy, multiple sclerosis and brain aging, as well as clinical immune intervention methods, based on fact that neuroinflammation is the common mechanism of many major brain diseases. These series of research achievements have broad application prospects in the diagnosis and treatment of brain diseases.
Introduction to Liu Qiang
Professor and Ph.D supervisor
Dr. Liu Qiang, Professor of the General Hospital of Tianjin Medical University, Tianjin Specially Appointed Professor. He has successively obtained a bachelor's and Master's degree in Clinical Medicine from Nanjing Medical University, a doctoral degree from Barrow Institute of Neurology in the United States, and completed postdoctoral research in immunology in Barrow. After returning to China, he joined the Department of Neurology, General Hospital of Tianjin Medical University to engage in clinical and scientific research. He served as the director of the Department of Neurodegenerative Diseases of Tianjin Institute of Neurology and a member of the cerebrovascular disease group of the Neurology Branch of the Chinese Medical Association. His main research direction is the immune mechanism and clinical intervention of brain diseases. He won the "Best Citation Award of Thesis", "First Prize of Tianjin Natural Science" and other awards from Chinese Stroke Association. In the past five years, he has published 20 SCI articles in Cell, Nature Neuroscience, Immunity, Science Translational Medicine, Journal of Experimental Medicine and other journals as corresponding authors.