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. 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 landmark Nature paper by Jonathan Kipnis and his postdoctoral fellow Antoine Louveau was published in 2015. By 2017, this paper was cited nearly 600 times, putting it in the 99th percentile for articles published that year. His discovery of meningeal lymphatic vessels has attracted attention from many sources, and was touted as a scientific breakthrough in lists such as 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. Business Insider highlighted this as the biggest discovery ever made in Virginia.
Other discoveries
Other high-profile research has included the 2015 discovery that the immune system directly affects social behavior and that IFN-gamma is necessary for social development. This expands upon his work as a graduate student, when he discovered that mice lacking T-cells had cognitive impairments. He is the senior author of a 2015 paper describing how CD4+ T-cells protect and repair neurons after injury to the spinal cord and brain. A collaboration with Kodi Ravichandran characterized the generation of neurons in adult brains and the removal of dead neurons by phagocytic cells. In 2016, he was the senior author on a paper identifying 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. In mice, these meningeal ILC2 cells were activated by IL-33 after spinal cord injury.
Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, Derecki NC, Castle D, Mandell JW, Lee KS, Harris TH, Kipnis J. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015 Jul 16;523:337-41..
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. Unexpected role of interferon-γ in regulating neuronal connectivity and social behaviour. Nature Jul 13;535:425-429..
Sandro 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. Functional aspects of meningeal lymphatics in ageing and Alzheimer's disease. Nature. Aug;560:185-191