Mural cells interact with macrophages in the dura mater to regulate CNS immune surveillance.

The central nervous system (CNS) tightly regulates access of circulating immune cells. Immunosurveillance is therefore managed in the meninges at the borders of the CNS. Here, we demonstrated that mural cells, which include pericytes and smooth muscle cells, decreased coverage around blood vessels in the dura, the outermost layer of the meninges, and upregulated gene pathways involved in leukocyte migration in presymptomatic experimental autoimmune encephalomyelitis (EAE).

Improving thymus implantation for congenital athymia with interleukin-7.

Objectives: Thymus implantation is a recently FDA-approved therapy for congenital athymia. Patients receiving thymus implantation develop a functional but incomplete T cell compartment. Our objective was to develop a mouse model to study clinical thymus implantation in congenital athymia and to optimise implantation procedures to maximise T cell education and expansion of naïve T cells.

Prolonged STAT1 activation in neurons drives a pathological transcriptional response.

Neurons require physiological IFN-γ signaling to maintain central nervous system (CNS) homeostasis, however, pathological IFN-γ signaling can cause CNS pathologies. The downstream signaling mechanisms that cause these drastically different outcomes in neurons has not been well studied. We hypothesized that different levels of IFN-γ signaling in neurons results in differential activation of its downstream transcription factor, signal transducer and activator of transduction 1 (STAT1), causing varying outcomes.

Amplified Gliosis and Interferon-Associated Inflammation in the Aging Brain following Diffuse Traumatic Brain Injury.

Traumatic brain injury (TBI) is associated with chronic psychiatric complications and increased risk for development of neurodegenerative pathology. Aged individuals account for most TBI-related hospitalizations and deaths. Nonetheless, neurobiological mechanisms that underlie worsened functional outcomes after TBI in the elderly remain unclear.

Astrocyte immunosenescence and deficits in interleukin 10 signaling in the aged brain disrupt the regulation of microglia following innate immune activation.

Microglia, the innate immune cells of the brain, develops a pro-inflammatory, "primed" profile with age. Using single-cell RNA-sequencing, we confirmed hippocampal microglia of aged mice (18 m.o.

Traumatic Brain Injury Causes Chronic Cortical Inflammation and Neuronal Dysfunction Mediated by Microglia.

Traumatic brain injury (TBI) can lead to significant neuropsychiatric problems and neurodegenerative pathologies, which develop and persist years after injury. Neuroinflammatory processes evolve over this same period. Therefore, we aimed to determine the contribution of microglia to neuropathology at acute [1 d postinjury (dpi)], subacute (7 dpi), and chronic (30 dpi) time points.

Interleukin-1 receptor on hippocampal neurons drives social withdrawal and cognitive deficits after chronic social stress.

Chronic stress contributes to the development of psychiatric disorders including anxiety and depression. Several inflammatory-related effects of stress are associated with increased interleukin-1 (IL-1) signaling within the central nervous system and are mediated by IL-1 receptor 1 (IL-1R1) on several distinct cell types. Neuronal IL-1R1 is prominently expressed on the neurons of the dentate gyrus, but its role in mediating behavioral responses to stress is unknown.

Forced turnover of aged microglia induces an intermediate phenotype but does not rebalance CNS environmental cues driving priming to immune challenge.

Microglia are the resident innate immune cells of the central nervous system. Limited turnover throughout the lifespan leaves microglia susceptible to age-associated dysfunction. Indeed, we and others have reported microglia develop a pro-inflammatory or "primed" profile with age, characterized by increased expression of inflammatory mediators (e.