Jonathan Kipnis

Last updated
Jonathan Kipnis
Jonathan Kipnis Headshot.jpg
NationalityIsraeli, American
Alma mater
Known fordiscovery of brain lymphatic vessels
Scientific career
Fields Neuroimmunology
Institutions
Doctoral advisor Michal Schwartz
Website Lab website

Jonathan Kipnis is a neuroscientist, immunologist, and professor of pathology and immunology at the Washington University School of Medicine. [1] His lab studies interactions between the immune system and nervous system. [2] He is best known for his lab's discovery of meningeal lymphatic vessels in humans and mice, which has impacted research on neurodegenerative diseases such as Alzheimer's disease and multiple sclerosis, [3] neuropsychiatric disorders, such as anxiety, and neurodevelopmental disorders such as autism and Rett syndrome.

Contents

Early life and education

Kipnis was born into a Jewish family in Tbilisi, Georgia. His father and maternal grandmother were both physicians and his mother was an academic with a focus in Russian literature and language. Surrounded by physicians, Kipnis knew from a young age that he wanted to cure diseases. [4] He received his undergraduate degree in biology at Tel Aviv University in Ramat Aviv, Israel [5] in 1998, and his Master's in neurobiology at the Weizmann Institute of Science in Rehovot, Israel in 1999. [5]

For his graduate training, Kipnis remained at the Weizmann Institute of Science. He first worked with Moshe Oren in cancer immunology, [6] but was inspired by Michal Schwartz, to pursue a PhD in neuroimmunology. [5] He joined Schwartz's lab the year that they discovered the therapeutic benefit of T cells in spinal cord and brain injury, a pioneering finding that began the study of the protective roles of autoimmunity in CNS disease. [7] This was the beginning of Kipnis' career exploring the connections between the brain and the immune system. [8]

In the Schwartz Lab, Kipnis' work focused on T cell based autoimmune reactions in CNS injury and neurodegeneration. [9] Kipnis elucidated the pleiotropic roles of regulatory T cells in CNS injury versus CNS homeostasis. [10] By depleting naturally occurring regulatory T cells after CNS injury, he was able to improve neuronal survival in mice. [10] However, by up-regulating effector autoimmune T cells through immunization with CNS antigen, he was able to improve recovery after CNS injury. These results showed that the immune system's intrinsic mechanisms to protect against autoimmunity, might not be beneficial when insults demand autoimmune effector function for tissue maintenance. [10]

Kipnis remained at the Weizmann for his postdoctoral training in Schwartz's lab. In this period he and other members of the lab, discovered that brain antigen specific T cells play a role in neurogenesis and cognitive functions, such as memory and spatial learning. [11] This was one of the seminal findings showing that the immune system, through T cells, plays a role in cognition and brain homeostasis. [12]

Career and research

Kipnis joined the University of Virginia School of Medicine (UVA) in 2007, where he later became a Harrison Distinguished Professor and chair of the department of neuroscience. He also directed the Center for Brain Immunology and Glia (BIG Center) at UVA. [13] In 2019, he accepted an offer to join the Washington University School of Medicine faculty via the BJC Investigators Program. He is primarily appointed in the department of pathology and immunology, and secondarily in neurology, neuroscience, and neurosurgery. [1] Kipnis is also a Gutenberg Forschungskolleg Fellow and supervises a working group at the University of Mainz. [14]

Meningeal lymphatic vessels

Kipnis is credited with the 2014 discovery of meningeal lymphatic vessels, a recently discovered network of conventional lymphatic vessels located parallel to the dural sinuses and meningeal arteries of the mammalian central nervous system (CNS). As a part of the lymphatic system, the meningeal lymphatics are responsible for draining immune cells, small molecules, and excess fluid from the CNS and into the deep cervical lymph nodes. While it was initially believed that both the brain and meninges were devoid of lymphatic vasculature, the 2015 Nature paper by Jonathan Kipnis and his postdoctoral fellow Antoine Louveau reporting their discovery was cited more than 3000 times by 2022 [15]

His discovery of meningeal lymphatic vessels was included in Scientific American's "Top 10 Science Stories of 2015", Science Magazine's "Breakthrough of the Year", Huffington Post's "Eight Fascinating Things We Learned About the Mind in 2015" and the National Institutes of Health's director Francis Collins year end review. [2] [16]

Cytokines and behavior

Other research has included the 2015 discovery that the immune system directly affects social behavior and that IFN-gamma is necessary for social development. [17] [18] This expands upon his work as a graduate student, when he discovered that mice lacking T-cells had cognitive impairments. [13] [19]

His lab also elucidated the role of meningeal gamma delta (γδ) T cells in anxiety behavior,. [20] [21] finding that γδ T cells are resident in high numbers in the meningeal immune compartment, and that they actively transcribe the cytokine IL-17a at homeostasis. [22] They further discovered that the release of IL-17a from γδ T cells was correlated with anxiety behavior in mice, finding high expression of IL-17a receptor in the prefrontal cortex glutamatergic neurons, and discovered that when they knocked down IL-17a receptor in cortical glutamatergic neurons, this recapitulated the anxiety phenotype in mice. [23]

He and his group in 2015 investigated CD4+ T-cells protection and repair of neurons after injury to the spinal cord and brain. [24] A collaboration with Kodi Ravichandran characterized the generation of neurons in adult brains and the removal of dead neurons by phagocytic cells. [25]

In 2016, and his group identified type 2 innate lymphocytes in the meninges near the lymphatic vessels his lab previously discovered. These cells have previously have been found in the gut, which suggests a link between the brain and the microbiome. [26] In mice, these cells were activated by IL-33 after spinal cord injury. [27]

Awards and honors

Kipnis' work has been funded by the Simons Foundation Autism Research Initiative, [28] National Institutes of Health, the Hartwell Foundation, and the Cure Alzheimer's Fund. [13] In 2018, he was awarded the NIH's prestigious Director's Pioneer Award and $5.6 million in additional research funding. [29]

Controversies

Kipnis has drawn fire for discouraging a former graduate student from reporting allegations of sexual misconduct towards her supervising post-doctoral candidate, confirmed by screenshotted text messages, and did not report the incident to Title IX investigators, stating "You don’t need [an] investigation now, even though you will most probably win." [33] While initially covered by the Washington University student newspaper, [34] this incident was later corroborated in an independent investigation by Stat News. [33] Emails with lab members shared with Stat News also revealed concerns about the Kipnis lab’s drinking culture, which were the subject of a university investigation. Per the Stat News report, there has been controversy about the university potentially mishandling the case, evidenced by a letter from the medical school dean describing Kipnis as supportive and prompt in his response and that failure to reach out to Title IX office was the result of incorrect advice from a program administrator as well as lax enforcement of Washington University School of Medicine's mandatory reporting system.

Select publications

YearTitle [35] PublicationAuthor(s)Volume/Issue Citation
2021Functional characterization of the dural sinuses as a neuroimmune interfaceCellRustenhoven 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.10.1016/j.cell.2020.12.040
2021Skull and vertebral bone marrow are myeloid cell reservoirs for the meninges and CNS parenchymaScienceCugurra 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.10.1126/science.abf7844
2019Bypassing the blood-brain barrierScienceRustenhoven J, Kipnis J.10.1126/science.aay0479
2018Functional aspects of meningeal lymphatics in ageing and Alzheimer's diseaseNatureSandro Da Mesquita, Antoine Louveau, Andrea Vaccari, Igor Smirnov, R. Chase Cornelison, Kathryn M. Kingsmore, Christian Contarino, Suna Onengut-Gumuscu, Emily Farber, Daniel Raper, Kenneth E. Viar, Romie D. Powell, Wendy Baker, Nisha Dabhi, Robin Bai, Rui Cao, Song Hu, Stephen S. Rich, Jennifer M. Munson, M. Beatriz Lopes, Christopher C. Overall, Scott T. Acton & Jonathan Kipnis.doi:10.1038/s41586-018-0368-8
2016Unexpected role of interferon-γ in regulating neuronal connectivity and social behaviourNatureFiliano 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.doi:10.1038/nature18626
2015Structural and functional features of central nervous system lymphatic vesselsNatureLouveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, Derecki NC, Castle D, Mandell JW, Lee KS, Harris TH, Kipnis J.doi:10.1038/nature14432

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References

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  9. ↑ Schwartz, Michal; Kipnis, Jonathan (2005-06-15). "Protective autoimmunity and neuroprotection in inflammatory and noninflammatory neurodegenerative diseases". Journal of the Neurological Sciences. 233 (1–2): 163–166. doi:10.1016/j.jns.2005.03.014. ISSN   0022-510X. PMID   15949502. S2CID   549851.
  10. 1 2 3 Kipnis, Jonathan; Mizrahi, Tal; Hauben, Ehud; Shaked, Iftach; Shevach, Ethan; Schwartz, Michal (2002-11-26). "Neuroprotective autoimmunity: naturally occurring CD4+CD25+ regulatory T cells suppress the ability to withstand injury to the central nervous system". Proceedings of the National Academy of Sciences of the United States of America. 99 (24): 15620–15625. Bibcode:2002PNAS...9915620K. doi: 10.1073/pnas.232565399 . ISSN   0027-8424. PMC   137766 . PMID   12429857.
  11. ↑ Ziv, Yaniv; Ron, Noga; Butovsky, Oleg; Landa, Gennady; Sudai, Einav; Greenberg, Nadav; Cohen, Hagit; Kipnis, Jonathan; Schwartz, Michal (February 2006). "Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood". Nature Neuroscience. 9 (2): 268–275. doi:10.1038/nn1629. ISSN   1097-6256. PMID   16415867. S2CID   205430936.
  12. ↑ "The vital link between your immune system and brain". www.macleans.ca. Retrieved 2021-01-04.
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  14. ↑ "Newsdetail - Universitätsmedizin Mainz - 165". 22 October 2015. Retrieved 22 December 2016.
  15. ↑ Louveau, Antoine; Smirnov, Igor; Keyes, Timothy J.; Eccles, Jacob D.; Rouhani, Sherin J.; Peske, J. David; Derecki, Noel C.; Castle, David; Mandell, James W.; Lee, Kevin S.; Harris, Tajie H.; Kipnis, Jonathan (16 July 2015). "Structural and functional features of central nervous system lymphatic vessels". Nature. 523 (7560): 337–341. Bibcode:2015Natur.523..337L. doi:10.1038/nature14432. PMC   4506234 . PMID   26030524.
  16. ↑ "Media coverage of our discoveries" . Retrieved 22 December 2016.
  17. ↑ "Shocking New Role Found for the Immune System: Controlling Social Interactions". 13 July 2016. Retrieved 22 December 2016.
  18. ↑ Filiano, Anthony J.; Xu, Yang; Tustison, Nicholas J.; Marsh, Rachel L.; Baker, Wendy; Smirnov, Igor; Overall, Christopher C.; Gadani, Sachin P.; Turner, Stephen D.; Weng, Zhiping; Peerzade, Sayeda Najamussahar; Chen, Hao; Lee, Kevin S.; Scott, Michael M.; Beenhakker, Mark P.; Litvak, Vladimir; Kipnis, Jonathan (21 July 2016). "Unexpected role of interferon-γ in regulating neuronal connectivity and social behaviour". Nature. 535 (7612): 425–429. Bibcode:2016Natur.535..425F. doi:10.1038/nature18626. PMC   4961620 . PMID   27409813.
  19. ↑ Kipnis, Jonathan; Cohen, Hagit; Cardon, Michal; Ziv, Yaniv; Schwartz, Michal (25 May 2004). "T cell deficiency leads to cognitive dysfunction: Implications for therapeutic vaccination for schizophrenia and other psychiatric conditions". PNAS. 101 (21): 8180–8185. Bibcode:2004PNAS..101.8180K. doi: 10.1073/pnas.0402268101 . PMC   419577 . PMID   15141078.
  20. ↑ Alves de Lima, Kalil; Rustenhoven, Justin; Da Mesquita, Sandro; Wall, Morgan; Salvador, Andrea Francesca; Smirnov, Igor; Martelossi Cebinelli, Guilherme; Mamuladze, Tornike; Baker, Wendy; Papadopoulos, Zach; Lopes, Maria Beatriz (November 2020). "Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons". Nature Immunology. 21 (11): 1421–1429. doi:10.1038/s41590-020-0776-4. ISSN   1529-2916. PMC   8496952 . PMID   32929273. S2CID   221723200.
  21. ↑ "Immune Cell Signaling to the Brain Regulates Anxiety-Like Behaviors". GEN - Genetic Engineering and Biotechnology News. 2020-09-16. Retrieved 2021-01-03.
  22. ↑ "Immune system may trigger anxiety in response to infection". www.medicalnewstoday.com. 2020-09-23. Retrieved 2021-01-03.
  23. ↑ "Immune Cell and Its Cytokine Control Exploratory Behavior in Mice". The Scientist Magazine®. Retrieved 2021-01-03.
  24. ↑ Walsh, James T.; Hendrix, Sven; Boato, Francesco; Smirnov, Igor; Zheng, Jingjing; Lukens, John R.; Gadani, Sachin; Hechler, Daniel; Gölz, Greta; Rosenberger, Karen; Kammertöns, Thomas; Vogt, Johannes; Vogelaar, Christina; Siffrin, Volker; Radjavi, Ali; Fernandez-Castaneda, Anthony; Gaultier, Alban; Gold, Ralf; Kanneganti, Thirumala-Devi; Nitsch, Robert; Zipp, Frauke; Kipnis, Jonathan (2 February 2015). "MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4". J Clin Invest. 125 (2): 699–714. doi:10.1172/JCI76210. PMC   4319416 . PMID   25607842.
  25. ↑ "Researchers helps explain how the adult brain cleans out dead brain cells and produces new ones". 10 August 2011. Retrieved 22 December 2016.
  26. ↑ "UVA discovers powerful defenders of the brain -- with big implications for disease" . Retrieved 22 December 2016.
  27. ↑ Gadani, Sachin P.; Smirnov, Igor; Smith, Ashtyn T.; Overall, Christopher C.; Kipnis, Jonathan (16 December 2016). "Characterization of meningeal type 2 innate lymphocytes and their response to CNS injury". The Journal of Experimental Medicine. 214 (2): 285–296. doi:10.1084/jem.20161982. PMC   5294864 . PMID   27994070.
  28. ↑ "SFARI" . Retrieved 22 December 2016.
  29. ↑ "UVA researcher wins national award, funding". Archived from the original on 2018-10-04. Retrieved 4 October 2018.
  30. ↑ . January 13, 2016 http://media.mindinstitute.org/video/graphics/dls/2016/kipnis_bioabstract.pdf . Retrieved 2020-01-15.{{cite web}}: Missing or empty |title= (help)
  31. ↑ "UVA's Jonathan Kipnis Receives Prestigious NIH Director's Pioneer Award". UVA Today. 2018-10-02. Retrieved 2021-01-04.
  32. ↑ "National Academy of Medicine Elects 100 New Members". National Academy of Medicine. 17 October 2022. Retrieved 23 November 2022.
  33. 1 2 "'I'm just disgusted': How alleged sexual misconduct stole one student's passion for academic science". STAT News. 2023-01-24. Retrieved 2023-01-24.
  34. ↑ "Alleged sexual misconduct and support system failures cause graduate student to drop her WU PhD degree - Student Life". Student Life - The independent newspaper of Washington University in St. Louis. 2022-12-07. Retrieved 2022-12-08.
  35. ↑ "Kipnis J PubMed Publications" . Retrieved June 9, 2023.
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