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An αHER2 antibody–neuraminidase conjugate, which selectively targets the removal of sialic acids from glycans on breast cancer cells, bypasses a glycoimmune checkpoint and enhances tumor cell killing by the host immune system.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Inflammatory and degenerative processes are thought to play a role in the pathophysiology of multiple sclerosis. Here, the authors identified twenty serum proteins associated with increased clinical and radiographic disease activity.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

The tau protein is theorized to spread transneuronally in Alzheimers disease, though this theory remains unproven in humans. Our simulations of epidemic-like protein spreading across human brain networks support this theory, and suggest the spreading dynamics are modified by β-amyloid

Transcriptomic analysis of astrocytes in the acute, subacute, and chronic phases after traumatic brain injury reveal an evolving dynamic shift from neuroinflammation to neurodegeneration, and to a limited extent, regeneration.

Expression of miR-124, a microglial microRNA, reduces disease in a mouse model of multiple sclerosis by inhibiting the transcription factor C/EBP-α and its downstream target PU.1.

Feedback control of a light-gated protein-protein interaction is used to deliver precisely tuned intracellular signals to cultured cells.

Novel immunomodulatory agents have considerably improved the treatment of multiple sclerosis in recent years, but inhibiting disease progression remains a central challenge. This article describes how advances in the understanding of the immunopathogenesis of multiple sclerosis have identified a range of novel targets for intervention and potential therapeutic agents acting at various steps in the pathogenic cascade, including different aspects of T-cell and B-cell function and neuroprotective strategies.

Transcriptome-wide analysis of differential expression (TRADE) is a broadly applicable tool for characterizing patterns of differential expression across the genome.

Integrating functional data with GWAS loci can help interpret the function of genetic variants associated with disease. Here the authors map cis and trans methylation QTL in CD4 + T cells from patients and colocalize with GWAS loci in order to interpret genetic variants associated with multiple sclerosis.

Using animal models and clinical samples, the authors report that glioblastoma metabolites activate the transcription factor aryl hydrocarbon receptor in tumor-associated macrophages to modulate their function and T cell immunity, promoting tumor growth.

Using more than 100 independent iPSC lines derived from patients with Alzheimer’s disease, the authors discovered loci associated with the neuronal production of amyloid β and confirmed their influence using RNA interference.

The scavenger receptor Scara1, expressed on microglia and macrophages, binds beta amyloid aggregates. In a mouse model of Alzheimer’s disease, the authors show that Scara1deficiency is associated with reduced clearance and increased deposition of aggregates in the brain, which results in early mortality.

The use of light to precisely control cellular behaviour is a challenge that has only recently begun to be addressed. Here, a genetically encoded light-control system is demonstrated in mammalian cells. Based on a reversible protein–protein interaction from the phytochrome signalling network of Arabidopsis thaliana, the system is used to reversibly translocate activators of the Rho-family GTPases to the plasma membrane with high temporal and spatial resolution.

Advanced paternal age associates with increased risk for psychiatric and developmental disorders in offspring. Here, Taylor et al. utilize parent-child trio exome sequencing data sets to estimate the contribution of paternal age-related de novo mutations to multiple disorders, including heart disease and schizophrenia.

Latency-associated peptide (LAP) is a membrane-bound form of TGF-β1. Here the authors show that LAP marks a subset of regulatory γδ T cells with innate gut-homing properties, which present antigen and induce CD4+ Foxp3+ in Peyer's patches and lamina propria.

Inglese et al. develop a predictive model that computes multi-regional statistical morpho-functional mesoscopic traits from T1-weighted magnetic resonance imaging scans. Their model reliably discriminates people with Alzheimer’s disease-related pathologies from those without.

Regulatory T cells may prevent acute and chronic rejection of organ transplants.

Three-dimensional imaging reveals the existence of GPCR domains at the plasma membrane of living cells. The molecular mechanism underlying this spatial organization is energetic coupling of receptors to the curvature of the plasma membrane.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

Single-cell whole-genome sequencing shows that 'foreground' cell-to-cell structural variation and alterations in copy number are associated with genomic diversity and evolution in triple-negative breast and high-grade serous ovarian cancers.

The gut microbiome has been implicated in several autoimmune disorders. Here, the authors study the gut microbiome of patients with multiple sclerosis, and find correlations between altered abundance of certain gut microorganisms and changes in expression of immune defence genes.

T_H17 cells contribute to anti-fungal and anti-bacterial adaptive immune responses. Sallusto and colleagues show that the transcription factor c-Maf has an immunoregulatory role in directing gene expression and tissue residency in human IL-10⁺ T_H17 cell subsets.

CD4⁺ T cells secreting interleukin-17 (T_H17) have diverse functions in modulating autoimmune diseases. Here the authors show via transcriptome analyses that a subset of human T_H 17 co-expressing interferon-γ (T_H1/17) has a molecular signature similar to “pathogenic” mouse T_H 17 but distinct from “non-pathogenic” mouse T_H 17.

Cyster and colleagues show that CD97–CD55 interactions, which trigger Gα₁₃–ARHGEF–Rho cytoskeletal signaling, are needed for proper MZ B cell positioning/retention in the spleen and for optimal antibody responses to T cell-independent antigens.

Many immune functions have been reported for γδ T cells, including the regulation of antibody responses. Here the authors show that CXCR5⁺ γδ T cells release Wnt ligands to initiate the T follicular helper cell differentiation program and promote antibody production.

Type 1 regulatory T cells control autoinflammatory diseases. In two linked papers, groups led by Kuchroo and Quintana demonstrate the role of the aryl hydrocarbon receptor in the differentiation of these cells.

Type 1 regulatory T cells control autoinflammatory diseases. In two linked papers, groups led by Kuchroo and Quintana demonstrate the role of the aryl hydrocarbon receptor in the differentiation of these cells.

The immune system plays a major part in neurodegenerative diseases. In this Review, Weiner considers the contributions of several components of the immune system in multiple neurodegenerative diseases and their potential as shared therapeutic targets across these diseases.

Analysis of peripheral mycobacteria-reactive CD4⁺ T cell receptor sequences from individuals infected with Mycobacterium tuberculosis shows a high degree of overlap between progressors and controllers, but points to some distinct clonotypes that are enriched in either group.