Search

Mapping of the neutrophil compartment using single-cell transcriptional data from multiple physiological and patological states reveals its organizational architecture and how cell state dynamics and trajectories vary during health, inflammation and cancer.

Contradictory results in animal atherosclerosis studies might partly explain limited translational efficacy, and also undermine the confidence of funding agencies, politicians, and the public in scientists and their research. A new guideline paper provides recommendations aimed at standardization of animal atherosclerosis studies to improve the reproducibility of this research.

Neutrophils infiltrate the ischemic brain. Here, the authors show a disease-stage dependent neutrophil diversification in neonatal brain injury; neutrophils aggravating tissue damage in the acute phase while promoting regeneration in the later stage.

Potthoff and colleagues present a MALDI-MSI-based method that integrates in-source brightfield and fluorescence microscopy, which allows for spatially-resolved analysis of lipids and metabolites at the (sub)cellular level.

Embryonal tumour with multilayered rosettes (ETMR) is a rare and aggressive paediatric brain tumour. Here, the authors analyse intratumour heterogeneity and the tumour microenvironment in ETMR using single-cell and spatial transcriptomics, in vitro cultures, and a 3D forebrain organoid model, finding important aspects – such as the communication with pericytes – for ETMR development and response to therapy.

Tumor-infiltrating neutrophils can have either pro-tumoral potential or anti-tumoral potential. Physical contact between heterogeneous neutrophils and tumor cells in the tumor microenvironment is now shown to facilitate the malignant progression of breast cancer.

This paper introduces msiFlow, an open-source software for scalable and reproducible end-to-end multimodal image analysis. Using msiFlow, the authors explore the molecular heterogeneity of leukocytes in infected tissues.

In this Review, Soehnlein and colleagues discuss the role of neutrophils in cardiovascular inflammation and repair, describing the effect of cardiovascular risk factors on neutrophil production and function, appraising the contribution of neutrophils to the different stages of atherosclerosis and its clinical manifestations, and highlighting the evolving therapeutic strategies for targeting neutrophil numbers, functional status and effector mechanisms.

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous and aggressive type of T-cell lymphoma. Here, the authors perform single-cell analyses of human and murine PTCL-NOS tumors, and identify a subtype defined by the loss of SMARCB1 that could be targeted with HDAC-inhibitor combination therapies.

Tissue infiltration of neutrophils is a key event of sterile and pathogen-induced inflammation; however, there is at present no non-invasive tool to visualize neutrophil dynamics in the body. Bouvain et al. develop a neutrophil-specific tracer that enables longitudinal imaging of neutrophil flux across the whole body.

Divangahi and colleagues report that β-glucan pretreatment before influenza A virus challenge can increase survival by inducing long-term reprogramming of neutrophils, promoting disease tolerance irrespective of viral load.

The contribution of inflammation to atherosclerosis is substantial, and is just beginning to be understood. In this Review, Soehnlein and Libby discuss how inflammation promotes atherosclerosis and its consequences, and how such processes could be targeted therapeutically. The potential pitfalls of targeting immune processes — namely the increased potential for infections — are also discussed, along with ways to modulate cardiovascular therapies in time and space to make them more effective.

Analysis of the transcriptional landscape of inflammatory neutrophils discloses specific transcription factor engagement at the bone marrow–to-blood and the blood-to-tissue transitions.

Tuz et al. report that stroke and myocardial infarction induce the release of neutrophil extracellular traps (NETs), triggering the loss of B cells and a decrease in immunoglobulin A secretion, and that inhibition of NETs prevents the loss of immunoglobulin A in mice and in patients with stroke.

This Review article discusses how the interaction of neutrophils, monocytes and macrophages is important for both initiating and terminating an inflammatory response. The authors describe the phagocyte-derived mediators involved in these interactions and highlight the therapeutic potential of targeting them.

Neutrophils are rapidly recruited to tissues in response to injury or infection, and they have mainly been studied in the context of acute inflammation. However, neutrophils can also be important contributors to chronic tissue inflammation. This Review discusses neutrophil function in the context of chronic inflammation and considers the potential of targeting these cells in chronic diseases.

The AIM2 inflammasome is activated by host and pathogen DNA. Work from the past 5 years indicates that the AIM2 inflammasome has an important role in advanced atherosclerosis driven by clonal haematopoiesis and possibly in atherosclerosis accelerated by acute infection. Therefore, the AIM2 inflammasome might be an important target for precision medicine.

Anisimov, Fang et al. report that in humans, genetic variants associated with higher TIE2 expression are predicted to confer a reduced risk of CAD; in mice, Tie2 expression in endothelial cells is atheroprotective, and in a subset of aortic fibroblasts, anti-inflammatory.

Mauersberger and colleagues show that loss of function of soluble guanylyl cyclase (sGC) in platelets increases plaque burden in atherosclerosis-prone Ldlr^−/− mice by increasing leukocyte adhesion to atherosclerotic plaques. While mouse platelets lacking sGC and human platelets from carriers of GUCY1A1 risk alleles showed reduced secretion of angiopoietin-1, pharmacological sGC stimulation increased platelet angiopoietin-1 release in vitro and reduced leukocyte recruitment and atherosclerotic plaque formation in vivo, suggesting sGC as a potential therapeutic target for the treatment and prevention of atherosclerosis.

High-dimensional datasets derived from time-resolved live imaging of leukocytes in mice were used to identify leukocyte identities and dynamic neutrophil states with high cellular resolution.

Accelerated atherosclerosis in a mouse model of clonal haematopoiesis is prevented by genetic interruption of AIM2 inflammasome activation or by inhibition of interleukin-1β.

Histone H4 is released from neutrophil extracellular traps and induces membrane lysis in vascular smooth muscle cells, leading to the destabilization of atherosclerotic plaques.

Circulating Ly6C^lo monocytes are thought to be derived from Ly6C^hi subset. Here the authors show that Notch signalling is activated in Ly6C^locells and is required for their differentiation, and that Notch ligands that initiate this signalling are provided by a subset of endothelial cells.

Cathelicidins are antimicrobial peptides that eliminate pathogens and contribute to the innate immune response. Here the authors show that neutrophil-derived LL-37/CRAMP induces platelet activation and promotes arterial thrombosis and thrombo-inflammation.

In this Roadmap, Stellos and colleagues discuss the mechanisms of cardiovascular system ageing and how the ageing of blood, vessels and heart relates to the decline in organ function, and highlight potential therapeutic interventions, challenges in ageing research and future directions for preclinical and clinical studies.