Key Roles for T Cell-derived IL-4 in Learning and Memory and for Bone Marrow Replacement in Amelioration of Rett Syndrome

Derecki, Noel Christopher, Department of Neuroscience, University of Virginia
Kipnis, Jonathan, Department of Neuroscience, University of Virginia
Lee, Kevin, Department of Neuroscience, University of Virginia

II Abstract Our grasp of the workings of the blood-brain barrier (BBB) has undergone a sea change in recent years. In fact, the brain is far-from-impenetrable to immune cells and their molecular mediators. Thus, the BBB can be thought of as a facilitator of communication rather than an impediment to it. A plethora of unanticipated factors, long considered germane only to the hematopoietic and immune systems, must now be taken into account when considering both healthy function and pathological dysfunction of the CNS. Accordingly, our understanding of what the term "neuroimmunology," encompasses, has also changed. Healthy physiological interactions are being uncovered that have implications far beyond the setting of frank pathology. Immune mediators have been shown to dictate CNS processes as fundamental as neuronal guidance, subtle as synaptic refinement and maintenance, and as complex as learning, memory, and higher cognitive function. Even within the realm of disease, our purview of is now considerably extended beyond "core" neuroinflammatory disorders such as MS. Many CNS pathologies have been demonstrated to feature immunity as a contributing factor, and the list is growing. Along these lines, we demonstrate here three things: (1) a critical role for a T cell-derived cytokine factor, interleukin (IL)-4, in learning and memory (2) a key role for anti-inflammatory meningeal myeloid cells-in the absence of T cells-as supportive of improved learning and memory in immunodeficient mice; (3) bone marrow transplant in amelioration of brain disease in a mouse model of the human neurodevelopmental pathology Rett syndrome. These results show the importance of immune cells and factors in support of normal cognitive function in health, and as critical effector cells in the treatment of CNS pathology.

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PHD (Doctor of Philosophy)
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