UCSF

Central nervous system (CNS) injuries are a leading cause of mortality and morbidity worldwide. Brain damage, including ischemic stroke and traumatic brain injury (TBI), initiates sterile inflammatory responses within CNS and the surrounding meningeal membranes. While the CNS is largely immune privileged at steady state, the adjacent meninges contain a large diversity of tissue-resident lymphocytes and, following brain damage, lymphocytes also infiltrate and take up residence within the brain parenchyma. The function of meningeal and brain-infiltrating lymphocytes and whether they beneficially or detrimentally impact the injury response after brain damage remains poorly defined. This study investigates how different lymphocyte populations impact wound healing and neurological sequelae after brain injury. First, using a mouse model of TBI, we identify a population of interferon-gamma (IFNg)-producing type 1 lymphocytes that infiltrates the thalamus at chronic timepoints following cortical injury and acts to restrict seizure susceptibility. Next, we investigate the role of meningeal type 2 innate lymphoid cells (ILC2s) in regulating the wound healing response to cortical photothrombotic (PT) injury. Finally, we review the reciprocal interactions between the nervous and immune systems, focusing on type 2 ‘allergic’ immunity, and highlighting the roles of type 2 neuroimmune crosstalk in both normal physiology and pathology. Together, this work further elucidates many key details about the impact of lymphocytes and other immune cells on the nervous system and reveals potential therapeutic opportunities that could be harnessed to treat human diseases, including brain injuries and related sequelae.