Jonathan Kipnis, Ph.D.
Director, Center for Brain Immunology and Glia (BIG)
Laboratory of Cellular and Molecular Neuroimmunology
Neuro-Immune interactions 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.
IL-33 (white) expression in the corpus callosum and choroid plexus of the healthy mouse brain. Also visible are myeloid cells (CX3CR1-GFP, green) and nuclei (dapi, blue).
Coronal sections of an uninjured (left) or injured (right; 21DPI) mouse spinal cord stained for GFAP (green). Reactive astrocytes are seen in the injured spinal cord defining the border of the unhealing glial scar.
SVZ Microglia (green) lying close to GFAP(red)+ Stem cells in the SVZ. DAPI in blue.
Whole mount meninges stained for T cells (red), macrophages (green) and lymphaticvessels (yellow).
Two-photon live imaging in the brain of mouse expressing GFP in microglia and macrophages (green) (CX3CR1 GFP). Cross section shows the skull bone (blue) and underneath it blood vessels (red) surrounded by meningeal macrophages and microglia.
A cluster of antigen presenting cells and T cells surrounding meningeal blood vessel. Blue – DAPI, Green – MHC II, Red – CD3.
Selected Recent Publications
Derecki N.C., Cardani A.N., Yang C.H., Quinnies K.M., Crihfield A., Lynch K.R., and 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.
Lu Z., Elliott M.R., Chen Y., Walsh J.T., Klibanov, A.I., Ravichandran K.S. and Kipnis J. (2011) Phagocytic activity of neuronal progenitors regulates adult neurogenesis. Nat Cell Biol. Jul 31;13(9):1076-83.
Derecki N.C., Cronk J.C., Lu Z., Xu E., Abbott S.B.G., Guyenet P.G. and Kipnis J. (2012) Wild type microglia arrest pathology in a mouse model of Rett syndrome. Nature. Mar 18;484(7392):105-9.
Walsh JT, Hendrix S, Boato F, Smirnov I, Zheng J, Lukens JR, Gadani SP, 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 Z, and 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 and Kipnis J. (2015) The glia-derived alarmin IL-33 orchestrates the post CNS injury immune response and promotes recovery. Neuron. Feb 18;85(4):703-9.
Cronk JC, Derecki NC, Ji E, Xu Y, Lampano A, Smirnov I, Baker W, Norris GT, Coddington N, Wolf Y, Klibanov AL, Harris TH, Jung S, Litvak V, and Kipnis J. (2015) Methyl-CpG Binding Protein 2 Regulates Microglia and Macrophage Gene Expression in Response to Inflammatory Stimuli. Immunity, 42, 679-691.
Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, Derecki NC, Castle D, Mandell JW, Lee KS, Harris TH, Kipnis J. (2015) Structural and functional features of central nervous system lymphatics. Nature, Jul 16;523(7560):337-41. doi: 10.1038/nature14432.
Filiano AJ, Xu Y, Tustison NJ, Marsh RL, Baker W, Smirnov I, Overall CC, Gadani SP, Turner SD, Weng Z, Peerzade SN, Chen H, Lee KS, Scott MM, Beenhakker MP, Litvak V, Kipnis J. (2016) Unexpected role of interferon-γ in regulating neuronal connectivity and social behaviour. Nature. Jul 21;535(7612):425-9.
Gadani SP, Smirnov I, Smith AT, Overall CC and Kipnis J (2017) Characterization of meningeal type 2 innate lymphocytes and their response to CNS injury. J Exp Med., Feb;214(2):285-296.
Cronk JC, Filiano AJ, Louveau A, Marin I, Marsh R, Ji E, Goldman DH, Smirnov I, Geraci N, Acton S, Overall CC, Kipnis J. (2018) Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia. J Exp Med. Jun 4;215(6):1627-1647
Norris GT, Smirnov I, Filiano AJ, Shadowen HM, Cody KR, Thompson JA, Harris TH, Gaultier A, Overall CC, Kipnis J. (2018) Neuronal integrity and complement control synaptic material clearance by microglia after CNS injury. J Exp Med. Jul 2;215(7):1789-1801.
Da Mesquita S, Louveau A, Vaccari A, Smirnov I, Cornelison RC, Kingsmore KM, Contarino C, Onengut-Gumuscu S, Farber E, Raper D, Viar KE, Powell RD, Baker W, Dabhi N, Bai R, Cao R, Hu S, Rich SS, Munson JM, Lopes MB, Overall CC, Acton ST, Kipnis J. (2018) Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease. Nature. Aug;560(7717):185-191.
Louveau A, Herz J, Alme MN, Salvador AF, Dong M, Viar K et al. (2018) CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nature Neuroscience. Sep;21(10): 1380-1391. 2018.
Department of Neuroscience at
University of Virginia
MR-4, Room 6124
Charlottesville, VA 22908