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Radiographics : a Review Publication of... Aug 2023Meningeal lesions can be caused by various conditions and pose diagnostic challenges. The authors review the anatomy of the meninges in the brain and spinal cord to...
Meningeal lesions can be caused by various conditions and pose diagnostic challenges. The authors review the anatomy of the meninges in the brain and spinal cord to provide a better understanding of the localization and extension of these diseases and summarize the clinical and imaging features of various conditions that cause dural and/or leptomeningeal enhancing lesions. These conditions include infectious meningitis (bacterial, tuberculous, viral, and fungal), autoimmune diseases (vasculitis, connective tissue diseases, autoimmune meningoencephalitis, Vogt-Koyanagi-Harada disease, neuro-Behçet syndrome, Susac syndrome, and sarcoidosis), primary and secondary tumors (meningioma, diffuse leptomeningeal glioneuronal tumor, melanocytic tumors, and lymphoma), tumorlike diseases (histiocytosis and immunoglobulin G4-related diseases), medication-induced diseases (immune-related adverse effects and posterior reversible encephalopathy syndrome), and other conditions (spontaneous intracranial hypotension, amyloidosis, and moyamoya disease). Although meningeal lesions may manifest with nonspecific imaging findings, correct diagnosis is important because the treatment strategy varies among these diseases. RSNA, 2023 and Quiz questions for this article are available through the Online Learning Center.
Topics: Humans; Posterior Leukoencephalopathy Syndrome; Meninges; Meningitis; Neuroimaging; Sarcoidosis; Meningeal Neoplasms; Magnetic Resonance Imaging
PubMed: 37535461
DOI: 10.1148/rg.230039 -
Nature Immunology Oct 2023Persistent exposure to antigen during chronic infection or cancer renders T cells dysfunctional. The molecular mechanisms regulating this state of exhaustion are thought...
Persistent exposure to antigen during chronic infection or cancer renders T cells dysfunctional. The molecular mechanisms regulating this state of exhaustion are thought to be common in infection and cancer, despite obvious differences in their microenvironments. Here we found that NFAT5, an NFAT family transcription factor that lacks an AP-1 docking site, was highly expressed in exhausted CD8 T cells in the context of chronic infections and tumors but was selectively required in tumor-induced CD8 T cell exhaustion. Overexpression of NFAT5 in CD8 T cells reduced tumor control, while deletion of NFAT5 improved tumor control by promoting the accumulation of tumor-specific CD8 T cells that had reduced expression of the exhaustion-associated proteins TOX and PD-1 and produced more cytokines, such as IFNɣ and TNF, than cells with wild-type levels of NFAT5, specifically in the precursor exhausted PD-1TCF1TIM-3CD8 T cell population. NFAT5 did not promote T cell exhaustion during chronic infection with clone 13 of lymphocytic choriomeningitis virus. Expression of NFAT5 was induced by TCR triggering, but its transcriptional activity was specific to the tumor microenvironment and required hyperosmolarity. Thus, NFAT5 promoted the exhaustion of CD8 T cells in a tumor-selective fashion.
Topics: Humans; Lymphocytic Choriomeningitis; Transcription Factors; CD8-Positive T-Lymphocytes; T-Cell Exhaustion; Persistent Infection; Tumor Microenvironment; Programmed Cell Death 1 Receptor; Lymphocytic choriomeningitis virus; Neoplasms
PubMed: 37709986
DOI: 10.1038/s41590-023-01614-x -
Nature Mar 2024Immune cells rely on transient physical interactions with other immune and non-immune populations to regulate their function. To study these 'kiss-and-run' interactions...
Immune cells rely on transient physical interactions with other immune and non-immune populations to regulate their function. To study these 'kiss-and-run' interactions directly in vivo, we previously developed LIPSTIC (labelling immune partnerships by SorTagging intercellular contacts), an approach that uses enzymatic transfer of a labelled substrate between the molecular partners CD40L and CD40 to label interacting cells. Reliance on this pathway limited the use of LIPSTIC to measuring interactions between CD4 T helper cells and antigen-presenting cells, however. Here we report the development of a universal version of LIPSTIC (uLIPSTIC), which can record physical interactions both among immune cells and between immune and non-immune populations irrespective of the receptors and ligands involved. We show that uLIPSTIC can be used, among other things, to monitor the priming of CD8 T cells by dendritic cells, reveal the steady-state cellular partners of regulatory T cells and identify germinal centre-resident T follicular helper cells on the basis of their ability to interact cognately with germinal centre B cells. By coupling uLIPSTIC with single-cell transcriptomics, we build a catalogue of the immune populations that physically interact with intestinal epithelial cells at the steady state and profile the evolution of the interactome of lymphocytic choriomeningitis virus-specific CD8 T cells in multiple organs following systemic infection. Thus, uLIPSTIC provides a broadly useful technology for measuring and understanding cell-cell interactions across multiple biological systems.
Topics: CD8-Positive T-Lymphocytes; Cell Communication; Dendritic Cells; Ligands; T-Lymphocytes, Regulatory; T Follicular Helper Cells; B-Lymphocytes; Germinal Center; Single-Cell Gene Expression Analysis; Epithelial Cells; Intestinal Mucosa; Lymphocytic choriomeningitis virus; Lymphocytic Choriomeningitis; Organ Specificity
PubMed: 38448581
DOI: 10.1038/s41586-024-07134-4