Jonathan Kipnis, Ph.D.

BJC Investigator & Alan A. and Edith L. Wolff Distinguished Professor
Pathology and Immunology
Professor
Neurology
Neuroscience

Immunology Program
Neurosciences Program
Molecular Genetics and Genomics Program
Molecular Cell Biology Program

  • 314-273-2288

  • Couch Building, West Wing, Room 1101

  • kipnis@wustl.edu

  • https://sites.wustl.edu/kipnis

  • Neuroimmunology; neuroscience; immunology; lymphatics; behavior; Alzheimer’s disease; neurodegeneration; glia; microglia; blood-brain barrier (BBB); meninges

  • We study complex interactions between the immune and nervous systems in health and disease

Research Abstract:

Our research group focuses on the complex interactions between the immune system and the central nervous system (CNS). The goal is to elucidate the cellular and molecular mechanisms underlying these interactions in neurodegenerative, neurodevelopmental, and mental disorders as well as in physiology (including healthy aging). We showed that the brain function is dependent, in part, on the function and integrity of the immune system and that immune molecules (cytokines) can play neuromodulatory roles. The fascination with immunity and its role in neurophysiology is what brought the team to a breakthrough discovery of meningeal lymphatic vessels that drain the CNS into the peripheral lymph nodes and thus serve as a physical connection between the brain and the immune system. This finding challenged the prevailing dogma of CNS being an “immune privileged organ” and opened new avenues to mechanistically study the nature of neuroimmune interactions under physiological and pathological conditions. The implications of this work are broad and range from Autism to Alzheimer’s disease through neuroinflammatory conditions, such as Multiple Sclerosis.

More information on our science, lab members and projects could be found on our website: https://sites.wustl.edu/kipnis

Selected Publications:


1. 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. doi: 10.1016/j.neuron.2015.01.013.

2. 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, April 21.

3. 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.

4. 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.

5. Louveau A, Herz J, Alme MN, Salvador AF, Dong MQ, Viar KE, Herod SG, Knopp J, Setliff JC, Lupi AL, Da Mesquita S, Frost EL, Gaultier A, Harris TH, Cao R, Hu S, Lukens JR, Smirnov I, Overall CC, Oliver G, Kipnis J. (2018) CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nat Neurosci. Oct;21(10):1380-1391. doi: 10.1038/s41593-018-0227-9. Epub 2018 Sep 17.

6. 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. doi: 10.1038/s41586-018-0368-8. Epub 2018 Jul 25.

7. Alves de Lima K, Rustenhoven J, Da Mesquita S, Wall M, Salvador AF, Smirnov I, Martelossi Cebinelli G, Mamuladze T, Baker W, Papadopoulos Z, Lopes MB, Cao WS, Xie XS, Herz J, Kipnis J. (2020) Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons. Nat Immunol. 2020 Nov;21(11):1421-1429. doi: 10.1038/s41590-020-0776-4. Epub 2020 Sep 14.PMID: 32929273

8. Rustenhoven J, Drieu A, Mamuladze T, de Lima KA, Dykstra T, Wall M, Papadopoulos Z, Kanamori M, Salvador AF, Baker W, Lemieux M, Da Mesquita S, Cugurra A, Fitzpatrick J, Sviben S, Kossina R, Bayguinov P, Townsend RR, Zhang Q, Erdmann-Gilmore P, Smirnov I, Lopes MB, Herz J, Kipnis J. (2021) Functional characterization of the dural sinuses as a neuroimmune interface. Cell. Feb 18;184(4):1000-1016.e27. doi: 10.1016/j.cell.2020.12.040. Epub 2021 Jan 27

9. Da Mesquita S, Papadopoulos Z, Dykstra T, Brase L, Farias FG, Wall M, Jiang H, Kodira CD, de Lima KA, Herz J, Louveau A, Goldman DH, Salvador AF, Onengut-Gumuscu S, Farber E, Dabhi N, Kennedy T, Milam MG, Baker W, Smirnov I, Rich SS; Dominantly Inherited Alzheimer Network, Benitez BA, Karch CM, Perrin RJ, Farlow M, Chhatwal JP, Holtzman DM, Cruchaga C, Harari O, Kipnis J. (2021) Meningeal lymphatics affect microglia responses and anti-Aβ immunotherapy. Nature. Apr 28. doi: 10.1038/s41586-021-03489-0. Online ahead of print.

10. Cugurra A, Mamuladze T, Rustenhoven J, Dykstra T, Beroshvili G, Greenberg ZJ, Baker W, Papadopoulos Z, Drieu A, Blackburn S, Kanamori M, Brioschi S, Herz J, Schuettpelz LG, Colonna M, Smirnov I, Kipnis J. (2021) Skull and vertebral bone marrow are myeloid cell reservoirs for the meninges and CNS parenchyma. Science. Jun 3:eabf7844. doi: 10.1126/science.abf7844. Online ahead of print.

Last Updated: 1/24/2022 5:19:40 PM

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