Jonathan Kipnis, Ph.D.
Assistant Professor
Neuro-Immune interactions
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Ph.D., 2004, Weizmann Institute of Science, Rehovot, Israel |
Neuro-Immune interactions in neurodegenerative and mental disorders - understanding of basic mechanisms and development of therapeutic vaccines
In my lab we are working on the interaction of the immune and nervous systems. Up until very recently, scientists assumed that the presence of immune system in the central nervous system (CNS) is a hallmark for undergoing pathological processes. However, new line of evidence supports the notion that immune assistance is required for a better neuronal survival following injury.
Moreover, we found recently that immune compromised mice exhibit behavioral and cognitive abnormalities as well as impaired neurogenesis as compared to mice with normally functioning immune system. Thus, animals that lack the population of T lymphocytes cannot perform cognitive tasks as well as normal animals do and are impaired in adult neurogenesis and neuronal plasticity. On the other hand, boost of immune response improves learning abilities in normal animals and accelerates neurogenesis process.
We are trying to elucidate on cellular and molecular levels the mechanism underlying these beneficial effects of immune cells in healthy and diseased CNS. We are also designing vaccines that promote neuronal survival and improve cognitive functions.
We are studying the role of immune system in the following conditions:
CNS injury and neurodegenerative diseases - neuronal regeneration, neuroprotection, and neurogenesis.
Models: spinal cord injury, optic nerve injury, brain injury, glaucoma, Alzheimer's Disease.
Mental conditions - cognition, neurogenesis, neuronal plasticity.
Models: age-related dementia, Alzheimer's Disease, Schizophrenia, Depression.
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| 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. |
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| 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. |
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| Primary neurons are grown in cultures and make spontaneous connections (synapses). Stimulations by T cells significantly increase the numbers of synapses. |
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| 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 Publications
Kipnis J., Hauben E., Mizrahi T., Shaked I., Shevach EM and Schwartz M. (2002) Neuronal Survival after Central Nervous System Injury is Improved by Depletion of CD4+CD25+ Regulatory T Cells and Worsened by Neonatal Tolerance to Myelin Proteins. Proc. Natl. Acad. Sci. USA, 26;99(24):15620-5.
Schwartz M. and Kipnis J., (2002) Autoimmunity on Alert: Naturally Occurring Regulatory CD4+CD25+ T cells as Part of the Evolutionary Compromise Between a "Need" and a "Risk". Trends Immunol., 23(11):530-4.
Kipnis J., Cohen H., Cardon M., Ziv Y. and Schwartz M (2004) T cell deficiency leads to cognitive impairment: Implications for therapeutic vaccination for schizophrenia and other psychiatric conditions. Proc. Natl. Acad. Sci. USA, 101:8180-8185
Kipnis J., Avidan H., Mordechay S., Lewitus G.M., Cardon M. and Schwartz M (2004) Dopamine, through the extracellular-regulated kinase pathway, downregulates CD4+CD25+ regulatory T cell activity: Implications for neurodegeneration. J Neurosci, 24(27):6133-43
Ziv, Y., Ron, N., Butovsky, O., Landa, G., Sudai, E., Greenberg, N., Cohen, H., Kipnis, J*., Schwarz, M., (2006) Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adults. Nat. Neurosci. Feb;9(2):268-75
Cohen H., Ziv Y., Cardon M., Kaplan Z., Gidron Y., Schwartz M. and Kipnis J. (2006) Adaptation to mental stress is autoimmune T-cell dependent and is suppressed by regulatory T cells. J Neurobiol, 66(6):552-63
Johnson T.V., Camras C.B. and Kipnis J. (2007) Bacterial DNA Confers Neuroprotection Following Optic Nerve Injury By Suppressing CD4+CD25+ Regulatory T-cell Activity. IOVS, Aug;48(8):3441-9
Lewitus G.M., Zhu J., Warren T., Xiong H., Hallworth R. and Kipnis J. (2007) Depletion of CD4+CD25+ Regulatory T Cells Results in Inhibition of Hippocampal Long-Term Potentiation by CD4+ T Cells. Eur. J. Neurosci., Sep; 26(6): 1399-406.
Liu J., Thomas J.V., Lin J., Bronich T.B., Caplan S., Persidsky Y., Gendelman H.E. and Kipnis J. (2007) T cell independent mechanism for Copolymer-1-induced neuroprotection. Eur. J. Immunol., Nov; 37 (11): 3143-54.
Brynskikh A., Warren T., Zhu J. and Kipnis J. (2008) Modulation of adaptive immunity influences cognition. Brain, Behavior, and Immunity, Jan 29; [Epub ahead of print].
Garg S., Banerjee R. and Kipnis J. (2008) Neuroprotective Immunity: T cell-derived Glutamate Endows Astrocytes with a Neuroprotective Phenotype. J Immunol. Mar 15; 180 (6): 3866-73.
Kipnis J, Derecki NC, Yang C, Scrable H. (2008) Immunity and cognition: what do age-related dementia, HIV-dementia and 'chemo-brain' have in common? Trends Immunol. Oct;29(10):455-63. Epub 2008 Sep 11.
Contact:
Jonathan Kipnis
mailto:kipnis@virginia.edu
Department of Neuroscience at
University of Virginia
MR-4, Room 6124
Box 801392
Charlottesville, VA 22908
Office:+1-434-982-3858
Lab:+1-434-982-3859
Cell:+1-434-964-6582