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 (out of over 75)
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.
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.
Derecki NC, Cronk JC, Lu Z, Xu E, Abbott SBG, Guyenet PG, 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. doi: 10.1172/JCI76210.
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) Mecp2: an unexpected regulator of macrophage gene expression and function. Immunity, 42, 679-691, April 21.
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 lymphatic vessels. Nature. 2015 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 13;535(7612):425-429. doi: 10.1038/nature18626.
Department of Neuroscience at
University of Virginia
MR-4, Room 6124
Charlottesville, VA 22908