Long noncoding RNA regulates antiviral immunity in humans.

Long noncoding RNAs (lncRNAs) have emerged as critical regulators of gene expression, yet their contribution to immune regulation in humans remains poorly understood. Here, we report that the primate-specific lncRNA is induced by influenza A virus and SARS-CoV-2 infection and coordinates the expression of interferon-stimulated genes (ISGs) that execute antiviral responses. depletion in human macrophages reduces histone acetylation at regulatory regions of ISG loci and attenuates ISG expression in response to microbial stimuli.

Copy number evolution in simple and complex tandem repeats across the C57BL/6 and C57BL/10 inbred mouse lines.

Simple sequence tandem repeats are among the most rapidly evolving compartments of the genome. Some repeat expansions are associated with mammalian disease or meiotic segregation distortion, yet the rates of copy number change across generations are not well known. Here, we use 14 distinct sublineages of the C57BL/6 and C57BL/10 inbred mouse strains, which have been evolving independently over about 300 generations, to estimate the rates of copy number changes in genome-wide tandem repeats.

Chronic stress primes innate immune responses in mice and humans.

Psychological stress (PS) is associated with systemic inflammation and accelerates inflammatory disease progression (e.g., atherosclerosis).

Silencing Myeloid Netrin-1 Induces Inflammation Resolution and Plaque Regression.

Rationale: Therapeutic efforts to decrease atherosclerotic cardiovascular disease risk have focused largely on reducing atherogenic lipoproteins, yet lipid-lowering therapies alone are insufficient to fully regress plaque burden. We postulate that arterial repair requires resolution of a maladaptive immune response and that targeting factors that hinder inflammation resolution will facilitate plaque regression. Objective: The guidance molecule Ntn1 (netrin-1) is secreted by macrophages in atherosclerotic plaques, where it sustains inflammation by enhancing macrophage survival and blocking macrophage emigration.

Inhibiting LXRα phosphorylation in hematopoietic cells reduces inflammation and attenuates atherosclerosis and obesity in mice.

Atherosclerosis and obesity share pathological features including inflammation mediated by innate and adaptive immune cells. LXRα plays a central role in the transcription of inflammatory and metabolic genes. LXRα is modulated by phosphorylation at serine 196 (LXRα pS196), however, the consequences of LXRα pS196 in hematopoietic cell precursors in atherosclerosis and obesity have not been investigated.

Wnt signaling enhances macrophage responses to IL-4 and promotes resolution of atherosclerosis.

Atherosclerosis is a disease of chronic inflammation. We investigated the roles of the cytokines IL-4 and IL-13, the classical activators of STAT6, in the resolution of atherosclerosis inflammation. Using mice, resolution was impaired, and in control mice, in both progressing and resolving plaques, levels of IL-4 were stably low and IL-13 was undetectable.

miR-33 Silencing Reprograms the Immune Cell Landscape in Atherosclerotic Plaques.

[Figure: see text].

Myocardial infarction accelerates breast cancer via innate immune reprogramming.

Disruption of systemic homeostasis by either chronic or acute stressors, such as obesity or surgery, alters cancer pathogenesis. Patients with cancer, particularly those with breast cancer, can be at increased risk of cardiovascular disease due to treatment toxicity and changes in lifestyle behaviors. While elevated risk and incidence of cardiovascular events in breast cancer is well established, whether such events impact cancer pathogenesis is not known.

Regulatory T Cells License Macrophage Pro-Resolving Functions During Atherosclerosis Regression.

Rationale: Regression of atherosclerosis is an important clinical goal; however, the pathways that mediate the resolution of atherosclerotic inflammation and reversal of plaques are poorly understood. Regulatory T cells (Tregs) have been shown to be atheroprotective, yet the numbers of these immunosuppressive cells decrease with disease progression, and whether they contribute to atherosclerosis regression is not known.

Objective: We investigated the roles of Tregs in the resolution of atherosclerotic inflammation, tissue remodeling, and plaque contraction during atherosclerosis regression.

The Y chromosome may contribute to sex-specific ageing in Drosophila.

Heterochromatin suppresses repetitive DNA, and a loss of heterochromatin has been observed in aged cells of several species, including humans and Drosophila. Males often contain substantially more heterochromatic DNA than females, due to the presence of a large, repeat-rich Y chromosome, and male flies generally have a shorter average lifespan than females. Here we show that repetitive DNA becomes de-repressed more rapidly in old male flies relative to females, and repeats on the Y chromosome are disproportionally mis-expressed during ageing.

The Drosophila Y Chromosome Affects Heterochromatin Integrity Genome-Wide.

The Drosophila Y chromosome is gene poor and mainly consists of silenced, repetitive DNA. Nonetheless, the Y influences expression of hundreds of genes genome-wide, possibly by sequestering key components of the heterochromatin machinery away from other positions in the genome. To test the influence of the Y chromosome on the genome-wide chromatin landscape, we assayed the genomic distribution of histone modifications associated with gene activation (H3K4me3) or heterochromatin (H3K9me2 and H3K9me3) in fruit flies with varying sex chromosome complements (X0, XY, and XYY males; XX and XXY females).

Neutrophil extracellular traps promote macrophage inflammation and impair atherosclerosis resolution in diabetic mice.

Neutrophil extracellular traps (NETs) promote inflammation and atherosclerosis progression. NETs are increased in diabetes and impair the resolution of inflammation during wound healing. Atherosclerosis resolution, a process resembling wound healing, is also impaired in diabetes.

Netrin-1 Alters Adipose Tissue Macrophage Fate and Function in Obesity.

Macrophages accumulate prominently in the visceral adipose tissue (VAT) of obese humans and high fat diet (HFD) fed mice, and this is linked to insulin resistance and type II diabetes. While the mechanisms regulating macrophage recruitment in obesity have been delineated, the signals directing macrophage persistence in VAT are poorly understood. We previously showed that the neuroimmune guidance cue netrin-1 is expressed in the VAT of obese mice and humans, where it promotes macrophage accumulation.

Single-Cell RNA Sequencing of Visceral Adipose Tissue Leukocytes Reveals that Caloric Restriction Following Obesity Promotes the Accumulation of a Distinct Macrophage Population with Features of Phagocytic Cells.

Obesity can lead to type 2 diabetes and is an epidemic. A major contributor to its adverse effects is inflammation of the visceral adipose tissue (VAT). Life-long caloric restriction (CR), in contrast, results in extended lifespan, enhanced glucose tolerance/insulin sensitivity, and other favorable phenotypes.

Single-cell analysis of fate-mapped macrophages reveals heterogeneity, including stem-like properties, during atherosclerosis progression and regression.

Atherosclerosis is a leading cause of death worldwide in industrialized countries. Disease progression and regression are associated with different activation states of macrophages derived from inflammatory monocytes entering the plaques. The features of monocyte-to-macrophage transition and the full spectrum of macrophage activation states during either plaque progression or regression, however, are incompletely established.

The chromatin landscape of Drosophila: comparisons between species, sexes, and chromosomes.

The chromatin landscape is key for gene regulation, but little is known about how it differs between sexes or between species. Here, we study the sex-specific chromatin landscape of Drosophila miranda, a species with young sex chromosomes, and compare it with Drosophila melanogaster. We analyze six histone modifications in male and female larvae of D.