Jonathan Kipnis
WashU Medicine in St. Louis
St. Louis, MO, USA
I have been studying the neuroimmune interactions in the healthy and diseased CNS for twenty five years (since my graduate school). During my graduate work I discovered the role of naturally occurring regulatory T cells in regulation of the immune response after CNS injury. During my graduate and a short post-doctoral training, I also became interested in the role of the immune system in cognition and behavior and have never stopped working on this topic. I showed that immune deficient mice exhibit impaired cognitive function as assessed in spatial learning and memory tasks, and that this impairment is reversible upon injection of T cells from wild type mice. In 2006, we identified the role of T cells in maintenance of adult neurogenesis. These studies allowed me to develop my own scientific niche, namely studying the role of the immune system in maintenance of the healthy CNS.
In my lab, we are continuing to concentrate on the roles of immunity in brain function. We identified IL-4 producing T cells in the meningeal spaces as major regulators of spatial learning and memory through their cognate receptor on neurons. We demonstrated the role of T cell derived IFNγ in regulating social behavior, again through signaling on neurons via their expressed IFNGR. More recently, we have identified another interesting population of meningeal immune cells, gamma/delta T cells, producing IL-17 and affecting anxiety behavior through neuronal IL-17R. In 2015 we have reported an unexpected presence of functional meningeal lymphatic vessels in the dura mater that drain macromolecules and immune cells from the CSF to the deep cervical lymph nodes. The connection between CSF and the deep cervical lymph nodes has been known for decades but the path for drainage of cells and protein was described as “unusual”. Our more recent data relates to the function of these meningeal lymphatic vessels as they regulate the perfusion rate of the brain parenchyma by the CSF. Impairment of meningeal lymphatics with age results in reduced brain perfusion and thus accumulation of debris within the brain, which may predispose to development of age-related dementia, including Alzheimer’s disease (AD). The main interest of the lab now is to understand molecular changes that occur in meningeal blood and lymphatic vasculature with age, how these changes affect meningeal immunity and how to counteract those changes to slow down detrimental consequences of aging. In our recently accepted manuscript, we have identified the anatomical structures used that allow bi-directional communication between the dura mater (where all the immune cells are located) and the brain. We have also identified skull bone marrow as a unique source for brain immunity and we are currently assessing the role of skull-derived immune cells in brain’s health and in age-related neurodegenerative disorders.
I have been lucky to train many exceptional graduate students and outstanding postdoctoral fellows in my lab over the past ~18 years. I have graduated 10 PhD students (3 of whom are MSTPs) and several of my ex-postdoctoral fellows are now holding faculty positions in major institutions and in industry. My group is currently composed of six graduate students (two of them are MSTP) and ten post-doctoral fellows. Students and post docs are assisted by technicians and veterinary staff. All the lab members are interdisciplinary trained in both neuroscience and immunology (and several are also experts in vascular biology). We are constantly pushing the technical frontiers in the lab through numerous collaborations.