In my lab at the University of Mainz we are working to understand the complex interactions between the immune and nervous systems in neuroinflammatory diseases, such as Multiple Sclerosis (MS). 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 required for optimal neuronal survival following CNS injury and for the higher brain function. This immune activity, however, needs to be under a tight control and when the control mechanisms fail, autoimmune attack on the brain takes place. Our recently discovery of meningeal lymphatic system that drains CNS (Louveau et al., Nature 2015), may provide an additional insight into the mechanism that regulates CNS autoimmunity.
Our goal is to elucidate the cellular and molecular mechanisms underlying the autoimmune attack on the CNS. We are using cutting edge technologies in neuroscience and immunology to address these challenging yet extremely interesting questions.
Gadani, S. P., Walsh, J. T., Lukens, J. R., and Kipnis, J. 2015. Dealing with Danger in the CNS: The Response of the Immune System to Injury. Neuron 87: 47-62.
Louveau, A., Smirnov, I., Keyes, T. J., Eccles, J. D., Rouhani, S. J., Peske, J. D., Derecki, N. C., Castle, D., Mandell, J. W., Lee, K. S., Harris, T. H., and Kipnis, J. 2015. Structural and functional features of central nervous system lymphatic vessels. Nature 523: 337-341.
Cronk, J. C., Derecki, N. C., Ji, E., Xu, Y., Lampano, A. E., Smirnov, I., Baker, W., Norris, G. T., Marin, I., Coddington, N., Wolf, Y., Turner, S. D., Aderem, A., Klibanov, A. L., Harris, T. H., 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.
Gadani, S. P., Walsh, J. T., Smirnov, I., Zheng, J., and Kipnis, J. 2015. The glia-derived alarmin IL-33 orchestrates the immune response and promotes recovery following CNS injury. Neuron 85: 703-709.
Walsh, J. T., Hendrix, S., Boato, F., Smirnov, I., Zheng, J., Lukens, J. R., Gadani, S., Hechler, D., Golz, G., Rosenberger, K., Kammertons, T., Vogt, J., Vogelaar, C., Siffrin, V., Radjavi, A., Fernandez-Castaneda, A., Gaultier, A., Gold, R., Kanneganti, T. D., Nitsch, R., Zipp, F., and Kipnis, J. 2015. MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4. J Clin Invest 125: 699-714.
Radjavi, A., Smirnov, I., Derecki, N., and Kipnis, J. 2014. Dynamics of the meningeal CD4(+) T-cell repertoire are defined by the cervical lymph nodes and facilitate cognitive task performance in mice. Mol Psychiatry 19: 531-533.
Derecki, N. C., Cronk, J. C., Lu, Z., Xu, E., Abbott, S. B., Guyenet, P. G., and Kipnis, J. 2012. Wild-type microglia arrest pathology in a mouse model of Rett syndrome. Nature 484: 105-109.
Lu, Z., Elliott, M. R., Chen, Y., Walsh, J. T., Klibanov, A. L., Ravichandran, K. S., and Kipnis, J. 2011. Phagocytic activity of neuronal progenitors regulates adult neurogenesis. Nat Cell Biol 13: 1076-1083.
Derecki, N. C., Cardani, A. N., Yang, C. H., Quinnies, K. M., Crihfield, A., Lynch, K. R., and Kipnis, J. 2010. Regulation of learning and memory by meningeal immunity: a key role for IL-4. J Exp Med 207: 1067-1080.