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Inflammation is a recognized component of many diseases, including atherosclerosis and its complications. IL-1β is a crucial cytokine promoting the inflammatory cascade. In the February 2017 issue of Nature Medicine, Furman et al. show that metabolites can trigger inflammation via inflammasome-dependent IL-1β production in elderly individuals. Intriguingly, caffeine is protective by offsetting this activation.

A γδ T cell–IL-3 signalling axis is defined that controls the allergen responsiveness of cutaneous sensory neurons, leading to evidence for an immune rheostat that governs sensory neuronal responses to allergens on first exposure.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

Here, Swirski and colleagues explore how the nervous and immune systems connect and collaborate to respond to internal and external stimuli. In particular, they consider how the exchange of information between both systems is vital for host physiology, in the context of both health and disease.

Macrophages are abundant in atherosclerotic plaques and are a pivotal cell type in plaque formation and progression. But how do they get there? Filip Swirski and his colleagues show that, contrary to most previous work that has emphasized the importance of monocyte recruitment from the blood, most macrophages in established lesions are generated by local macrophage proliferation, which depends on the SR-A scavenger receptor.

Myocardial infarction accelerates atherosclerosis through activation of the sympathetic nervous system, and the consequent release of haematopoietic stem and progenitor cells.

Yamazoe et al. show that B cell-derived autoantibodies contribute to the development of atrial fibrillation, suggesting that targeting the humoral immune response may represent a viable therapeutic approach.

Macrophages densely populate the arterial wall, yet their origin and homeostasis are poorly understood. Robbins and colleagues show that arterial macrophages arise from CX3CR1⁺ embryonic precursors and adult bone marrow–derived monocytes that colonize the tissue immediately after birth.

In this Review, Swirski and co-workers discuss how lifestyle factors modulate haematopoiesis and leukocyte migration in the context of cardiovascular homeostasis and disease, with particular focus on the role of the nervous system as the key executor connecting environmental influences to leukocyte behaviour.

Consumption of a high-fat diet leads to the progressive growth of atherosclerotic lesions. Two new studies document that, despite similar overall exposure to high-fat diet over a lifetime, an intermittent consumption of high-fat diet early in life accelerates atherosclerosis compared with continuous consumption of a high-fat diet. The mechanisms for accelerated atherosclerosis include reprogramming of macrophages and neutrophils.

Distinct brain regions differentially and rapidly tailor the leukocyte landscape during psychological stress, calibrating the ability of the immune system to respond to physical threats.

Interleukin-3 signalling from astrocytes to microglia readies microglia to defend against Alzheimer’s disease.

Myeloid cells contribute to the etiology of multiple sclerosis (MS), but the dynamics of myelopoiesis during disease progression is still unclear. Here the authors show, in both mouse models and clinical data, that myelopoiesis is differentially regulated via M-CSF modulation in different organs at distinct stages of MS, with diet and lifestyle being potential modifiers.

Studies in humans and mice show that myocardial infarction recruits monocytes to the brain’s thalamus, promoting sleep, which in turn restricts cardiac inflammation and sympathetic signalling and assists healing.

Infection by coagulase-positive Staphylococcus aureus (S. aureus) is the most common cause of acute endocarditis, a destructive and progressive condition of heart valves. Here, Peter Panizzi and his colleagues have developed a targeted, noninvasive fluorescence or positron emission technology imaging strategy that uses an engineered analog of prothrombin that can detect S. aureus in vivo in the endocarditic vegetations that form as a result of bacterial colonization.

Grune et al. show that hypokalemic mice develop spontaneous ventricular tachycardia after myocardial infarction, and they use this model to dissect the role of immune cells in arrhythmia: neutrophils increase ventricular tachycardia, partly by promoting reactive oxygen species production, whereas efferocytic macrophages play a protective role.

Serum MMP8 is increased in stress-susceptible mice following chronic stress and leads to brain structure and behavioural changes in mice.

Plaques are lipid-rich structures in the blood-vessel wall that can cause heart attacks or strokes if they rupture. It now seems that blood-cell fragments called platelets alter the function of immune cells in ways that accelerate plaque formation.

Nahrendorf and colleagues show that B cells in the bone marrow are an important source of the neurotransmitter acetylcholine, which limits hematopoiesis through modulating the signals produced by the bone marrow stromal niche during steady-state and emergency hematopoiesis.

Cellular composition and function are not clearly defined in heart failure after myocardial infarction. Here, using single cell and spatial transcriptomics in a MI-HF mouse model, the authors show that macrophages expressing Trem2 are found within the infarcts and this could be a useful biomarker.

In 2017, a cluster of papers have provided strong evidence in favour of the inflammation hypothesis in cardiovascular disease. From fundamental observations on clonal haematopoiesis to clinical evidence indicating that blocking an inflammatory cytokine mitigates heart disease, 2017 has been a watershed year.

Systemically injected lipid–polymer nanoparticles encapsulating small interfering RNA for silencing genes in bone-marrow endothelial cells of mice improved the healing of the mice after myocardial infarction.

Zhang et al. show that bone marrow fatty acid metabolism fuels expanded leukocyte production after myocardial infarction and, based on mouse, pig and human data, suggest that lipolysis in marrow adipocytes provides fatty acids to hematopoietic stem cells.

Here, the authors identify interleukin-3 as a predictive marker for severity and outcome of SARS-CoV-2 infection in a multi-center, prospective study and find that patients with severe COVID-19 have reduced circulating plasmacytoid dendritic cell levels compared to non-severe COVID-19 patients.

The beneficial effects of exercise on cardiovascular disease are linked to decreased inflammation through crosstalk between adipose tissue and hematopoietic progenitor cells in the bone marrow.

A multimodal imaging approach using a high-density lipoprotein-derived nanotracer with a perfluoro-crown ether payload enables myeloid cell dynamics to be studied in vivo in mouse models of atherosclerosis and myocardial infarction.

Sick heart and vessels skew hematopoiesis toward inflammatory myeloid cells. Rhode et al. show that hypertension, atherosclerosis and myocardial infarction cause endothelial dysfunction in bone marrow (BM), which in return causes overproduction of inflammatory myeloid cells and systemic leukocytosis in mice. This process is mediated by VEGF signaling, IL-6 and versican production by the BM endothelium.

This manuscript describes a new cerebral spinal fluid exit route via hundreds of skull channels, with the cranial bone marrow as a destination. In meningitis, bacteria hijack this path and alert hematopoietic stem cells residing in the skull marrow.

In vivo imaging of inflammation is crucial for detection and monitoring of many pathologies and noninvasive macrophage quantification has been suggested as a possible approach. Here Keliher et al. describe novel polyglucose nanoparticle tracers that are rapidly excreted by the kidney and with high affinity for macrophages in atherosclerotic plaques.

The authors describe microscopic channels that directly connect the skull marrow cavities with the meninges. Neutrophils originating from the skull marrow have a higher propensity to travel to the ischemic mouse brain than cells in the tibia.

In this Roadmap, Aggarwal and colleagues summarize current research and knowledge gaps on the relationship between sleep, circadian rhythms and cardiovascular resilience; highlight potential therapeutic targets and interventions for optimizing sleep and circadian rhythms to improve cardiovascular function and prevent disease; and outline research directions and opportunities, emphasizing the need for multidisciplinary collaboration.

A nanoparticle-based immunotherapy targeted to a protein responsible for signalling between monocytes and macrophages reduces plaque inflammation in atherosclerotic mice and appears to be safe in non-human primates.

Angiopoietin-like 4 protein (ANGPTL4) is a regulator of lipoprotein metabolism whose role in atherosclerosis has been controversial. Here the authors show that ANGPTL4 deficiency in haematopoietic cells increases atherogenesis by promoting myeloid progenitor cell expansion and differentiation, foam cell formation and vascular inflammation.

Kiss et al. review preclinical and clinical evidence illustrating how sleep impacts the nervous, metabolic and immune systems, ultimately influencing the development and progression of atherosclerotic cardiovascular disease.

In vivo silencing in specific cell types remains the main obstacle for therapeutic applications of siRNAs. Leuschner et al. now show that an optimized lipid nanoparticle delivers siRNA to inflammatory monocytes in mice and, when transporting CCR2 siRNA, has therapeutic effects in cardiovascular disease, cancer and transplant rejection.

Integrin β7-dependent Glp1r^high natural gut intraepithelial T lymphocytes that reside in the small intestine modulate dietary metabolism in mice by restricting the bioavailability of GLP-1.

The fragmentation of sleep in Apoe^−/− mice induces monocytosis and accelerated atherosclerosis due to a reduction in hypocretin that otherwise restricts bone marrow CSF1 availability.

In this Review, the authors discuss the cellular and molecular mechanisms of immunometabolism in heart failure and highlight potential approaches for non-invasive monitoring and for the treatment of patients with heart failure.

Activation of bone marrow hematopoietic stem cells by chronic stress raises circulating leukocyte levels and increases atherosclerotic plaque inflammation.

Damaged erythrocytes accumulate in various pathological conditions, such as hemolytic anemia, anemia of inflammation, and sickle cell disease. In mice challenged with damaged erythorcytes, a monocyte subset migrates to the liver (but not to the spleen), and this subset differentiates into a transient macrophage population that removes the damaged erythrocytes, thus preventing organ damage.

Stress modulates immune system function and systemic inflammation is linked to stress-related disorders, including depression. Russo and colleagues outline the neural circuits through which the CNS regulates immune cell function in peripheral tissues in response to stress and consider how these responses contribute to stress-related pathophysiology.

Recent studies have characterized complex interactions between resident and infiltrating immune cells in the heart and cardiac cells, including cardiomyocytes, fibroblasts and endothelial cells. This Review explores the role of immune cells in cardiac development and physiological function, as well as heart disease.