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McGavern and colleagues identified a CD8⁺ T cell population that expresses GZMK in ʽtau-richʼ brains, where it may play a protective role against neurodegeneration.

Microscopic imaging and biochemical studies show that sinuses in mouse and human form a highly dynamic surface that regulates fluid movement and immune cell surveillance via RAMP1-dependent regulation of smooth muscle contraction and RAMP2-dependent regulation of the sinus endothelial barrier.

Traumatic brain injury and stroke are commonly complicated by systemic infections, which impede recovery and lead to poor clinical outcomes. Using a mouse model, McGavern and colleagues show systemic microbial infections impair central nervous system revascularization and repair by a mechanism involving type I interferon signaling.

The central nervous system meninges have a dense network of yolk sac–derived macrophages that serve a sentinel role. McGavern and colleagues show that this meningeal niche is replenished by bone marrow–derived inflammatory monocytes, which alters meningeal immune reactions after subsequent immune challenge.

Meningeal vascular damage accompanies mild traumatic brain injury, which persists in a fraction of patients. McGavern and colleagues report that distinct myeloid cell subsets are temporally recruited to the wound site during tissue repair; however, re-injury at early time points impairs recovery.

In this study, Yu et al. found that a positive feedback loop between oxidized phosphatidylcholine and IL-1β promotes chronic neurodegeneration in the central nervous system and could be a contributing mechanism to progressive multiple sclerosis.

Bacteria that cause meningitis have been found to stimulate nerve fibres in the brain’s meninges to release a neuropeptide molecule that dampens the response of immune cells and aids bacterial invasion of the central nervous system.

Love and colleagues find an inhibitory function for CD3ζ ITAMs in response to low-affinity ligands, meaning that CD3ζ can perform a dual function in TCR signaling by playing a positive or negative role depending on the affinity of the TCR for its peptide ligand.

This Review describes the anatomical features of the central nervous system (CNS) barriers and focuses on the way in which the immune system responds to neurotropic viruses that establish latent or persistent infections in the CNS. It also discusses imaging technologies that can be used to understand viral entry and antiviral immune responses in the CNS.

Dural-associated lymphoid tissues are lymphoid structures around vascular hubs in the dura mater that sample antigens and rapidly support humoral immune responses after local pathogen challenge.

T follicular helper (Tfh) and T help type 1 (Th1) cells both arise from naïve CD4 T cells, but detailed knowledge of their differentiation remains incomplete. Here the authors pursue an in vivo CRISPR screen to identify genes, focusing on druggable targets, regulating Tfh versus Th1 to provide a resource for related studies, while also implicating HIF-1α and VHL in this regulation.

Long-lived, self-renewing ‘progenitor-like’ CD8⁺ T cells can arise during chronic viral infection or in cancer. Wu and colleagues identify the transcription factor TOX as essential to endow ‘stemness’ and long-term persistence in the face of chronic infection.

Choi et al. show that infiltrating CCR2⁺ monocytes, by provision of IL-6, instruct tissue-resident microglia to become ‘repair-associated microglia’ following intracerebral hemorrhage, promoting cerebrovascular repair and neurological recovery.

Yang and colleagues report that MAIT cells are present in the meninges where they play an essential role in repressing tissue ROS accumulation and preserving meningeal barrier integrity.

Nie et al. show that the transcription factor LRF, by upregulating expression of the integrin gene Itgb7, imprints thymic precursors of CD8αα⁺ intraepithelial lymphocytes for eventual seeding of the gut tissues.

IgA-secreting plasma cells that originate in the intestine are found in the meninges, where they protect the brain against pathogens.

Tuoqi Wu and colleagues show that the transcriptional repressor BACH2 is required early after chronic viral infection to enforce a stem-like fate in activated CD8⁺ T cells. BACH2 acts to suppress genes that lead to the exhausted cell state.

This study shows how different myeloid cell types contribute to damage and repair following cerebrovascular injury, a pathology common to many central nervous system disorders, and offers new therapeutic opportunities to improve clinical outcomes.

Single-nucleus transcriptomics defines a diverse set of immune and glial cells at the chronically inflamed leading edge of demyelinated white matter lesions in patients with multiple sclerosis.

To determine how T cell lineage fates are determined in the thymus, Singer and colleagues generated ‘FlipFlop’ mice with a functionally reversed T cell immune system that distinguishes TCR signal strength versus TCR signal duration.

The strength of TCR activation shapes T cell selection and differentiation. Here the authors show by modulating the number of activatory motifs in TCR complex that the strength of TCR signal is critical for the development of some T cell subsets but not for T cell effector functions or repertoire.

T. gondii crosses biological barriers using transcellular migration or within an infected migrating cell. Here, infection and lysis of endothelial cells in the brain vasculature is identified as a new route of access to the central nervous system.

Lazarevic and colleagues show that T-bet-dependent NKp46⁺ innate lymphoid cells reside within the meninges of the CNS and initiate meningeal inflammation, thereby facilitating T cell entry into parenchymal CNS tissues and contributing to neuroinflammation.

CD8⁺ T cells are shown to induce vascular leakage in acute viral meningitis not by killing specific target cells, but by recruiting neutrophils and monocytes to the blood–brain barrier.

Pandya et al. describe a protocol to differentiate human and mouse iPSCs into cells with the phenotype, transcriptional profile and functional properties of microglia. The treatment of murine intracranial malignant gliomas with these cells demonstrates their potential clinical use. These microglia-like cells will enable further studies into the role of microglia in health and disease.

Using long-term intravital photography to explore the cellular changes after compression-induced traumatic brain injury in a murine model, it is shown that parenchymal and meningeal inflammation as well as cell death can be modulated by topical treatment with purinergic receptor antagonists and glutathione.