Jonathan Kipnis, Ph.D.
Ph.D., 2004, Weizmann Institute of
Professor of Neuroscience
Director, Center for Brain Immunology and Glia (BIG)
Laboratory of Cellular and Molecular Neuroimmunology
in neurodegenerative, mental, cognitive and neurodevelopmental
disorders – understanding of basic mechanisms and development of novel
therapies and vaccines.
Kipnis Lab Website
In my lab we are working to better understand the complex interactions between the immune and nervous systems. Until very recently, scientists assumed that any activity of the immune system within or around the central nervous system (CNS) was a hallmark of pathology. However, multiple new lines of evidence support the notion that immune support is actually required for optimal neuronal survival following CNS injury.
In parallel, we recently showed that immune-compromised mice exhibit behavioral and cognitive abnormalities when compared to mice with normally-functioning immune systems. Animals that lack the population of unique T lymphocytes, or key molecular factors produced by these cells, are strikingly impaired in learning and memory tasks, adult neurogenesis, and neuronal plasticity. Moreover, a well-controlled boost of immune response improves learning abilities in normal animals and accelerates the process of neurogenesis.
Our goal is to elucidate the cellular and molecular mechanisms underlying the beneficial effects of immune cells in healthy and diseased CNS. On the therapeutic “frontline”, we are designing vaccines and developing novel therapies with a potential to promote neuronal survival, improve cognitive functions, and slow down progression of neurodegenerative, neurodevelopmental and cognitive disorders.
We are studying the following areas:
CNS injury and neurodegenerative diseases - neuronal regeneration, neuroprotection, and neurogenesis.
Models: stroke, spinal cord injury, optic nerve injury, brain injury, glaucoma, Alzheimer's Disease.
Cognitive and mental disorders – impairment of cognition, neurogenesis, and neuronal plasticity; glial biology.
Models: age-related dementia, chemo-brain, Alzheimer's Disease, schizophrenia, and depression.
To learn more about the role of immunity in cognitive function, take a look at this Scientific American Blog post on our research.
Neurodevelopmental disorders – neurogenesis, neuronal plasticity, synapse formation and maintenance, glial biology.
Models: autism spectrum disorders, Rett syndrome.
|Wild type and immune deficient (scid) mice were compared at cognitive task performance on Barnes Maze (the aim is to find a hidden box within the shortest time). Note the difference in the path length between the two strains.|
|Brains from wild type and immune deficient (scid) mice were analyzed for synapses using electron microscope. Note the difference in the numbers of synapses (marked by red arrow heads) between wild type and scid mice.|
|Primary neurons are grown in cultures and make spontaneous connections (synapses). Stimulations by T cells significantly increase the numbers of synapses.|
|Brains from wild type and immune deficient (scid) mice were analyzed for newly born neurons (green) and neural stem cells (red) using confocal microscope. Note the difference in the numbers of neuronal and neural progenitors between wild type and scid mice.|
Selected Recent Publications
Derecki NC, Cardani AN, Yang CH, Quinnies KM, Crihfield A, Lynch KR, Kipnis J. (2010) Regulation of learning and memory by meningeal immunity: a key role for IL-4. J Exp Med. May 10;207(5):1067-80. Epub 2010 May 3.
Lu Z, Elliott MR, Chen Y, Walsh J., Klibanov, AI, Ravichandran KS, Kipnis J. (2011) A novel phagocytic role for neural progenitors that regulates adult neurogenesis. Nat Cell Biol. Jul 31:13(9):1076-83.
Radjavi A, Smirnov I, Derecki N, Kipnis J. (2013) Dynamics of the meningeal CD4+ T-cell repertoire are defined by the cervical lymph nodes and facilitate cognitive task performance in mice. Mol Psychiatry. Jun 11. doi: 10.1038/mp.2013.79.
Walsh JT, Hendrix S, Boato F, Smirnov I, Zheng J, Lukens JR, Gadani S, Hechler D, Gölz G, Rosenberger K, Kammertöns T, Vogt J, Vogelaar C, Siffrin V, Radjavi A, Fernandez-Castaneda A, Gaultier A, Gold R, Kanneganti TD, Nitsch R, Zipp F, Kipnis J. (2015) MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4. J Clin Invest. Feb;125(2):699-714.
Gadani SP, Walsh JT, Smirnov I, Zheng J, Kipnis J. (2015) The Glia-Derived Alarmin IL-33 Orchestrates the Immune Response and Promotes Recovery following CNS Injury. Neuron. Feb 4. [Epub ahead of print]
Department of Neuroscience at
University of Virginia
MR-4, Room 6124
Charlottesville, VA 22908