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Understanding normal hematopoiesis is critical to understanding disease. Technological advances are driving insight into human hematopoiesis at unprecedented resolution. Integrating ‘-omics’ datasets with machine learning has yielded a high-resolution map of primary human bone marrow hematopoietic progenitor cells that supports the study of immune cell development, as well as the origins of disease.
DNA sensing for the purposes of innate immunity is tricky when the DNA sensor can easily become stuck on chromosomes during cell division. The mechanism by which the trapped DNA sensor is degraded — and how this process can be balanced with added immune protection — is now reported.
T cell- and antibody-based immunological protection are generally considered to function together, but data now show how T cells conferred by previous SARS-CoV-2 infection or two-dose vaccination can elicit heterologous protection in mice against subsequent SARS-CoV-2 infection, even in the absence of antibodies.
Granulosomes are novel complexes that feature an unexpected partnership between the tetraspanin CD63 and the inflammasome proteins NLRP3 and ASC. Granulosomes assemble on mast cell granules to propel them along microtubules to the plasma membrane for degranulation.
Drivers of persistent symptoms after acute COVID-19 remain largely unknown. Alterations in immune function, iron homeostasis and dysregulated erythropoiesis are described as treatable correlates of post-acute sequelae of COVID-19.
A landmark study reveals how Kupffer cells, resident macrophages of the liver, can promote antitumor immunity. Central to this function is ID3, a Kupffer cell lineage-determining factor. The findings provide new insights into cancer therapy.
Schäfer et al. discuss the application of computational methods that integrate single-cell and spatial multi-omics with existing biological knowledge to inform our understanding of immunological responses.
A study identifies an increase in the tissue-protective factor HB-EGF during the initial stage of multiple sclerosis (MS), which is actively turned off as the disease worsens.
Bacillus Calmette–Guérin (BCG) is the only available vaccine against tuberculosis. As well as being an effective vaccine against tuberculosis, BCG also provides off-target protection against various pathogens. Here, we report a mechanism for BCG-mediated cross-protection against influenza A virus (IAV), which requires a dialogue between the innate and adaptive immune memory systems.
In this study, we developed an adenoviral-vectored vaccine that targets the spike protein of BA.5 Omicron SARS-CoV-2. When nasally delivered in mice and hamsters, the vaccine stimulated mucosal antibody production and CD8+ T cell responses, and demonstrated protection against several SARS-CoV-2 strains, including the antigenically distant Omicron XBB.1.5 strain. Immune cell depletion studies showed that cross-reactive memory CD8+ T cells contribute to the cross-protection that is conferred by nasal vaccines against respiratory infection with antigenically shifted SARS-CoV-2 Omicron strains.
Visceral adipose tissue hosts at least two populations of mature FOXP3+ regulatory T cells, which together can preserve systemic metabolism and control inflammation.
Intratumoral regulatory T (Treg) cells can suppress antitumor immunity. Unlike in splenic Treg cells, the H3K9me2 demethylase JMDJ1 seems to be induced, and is required for this function, in the tumor microenvironment, and targeting it with a small-molecule inhibitor can suppress tumor growth in mice.
Understanding the ontogeny of conventional dendritic cells (cDCs) is a major aim in the field. The fate of progenitors of the recently described subsets of mouse cDC2s (cDC2A and cDC2B) is determined in the bone marrow.
The development of therapies for ischemic stroke requires a deep understanding of the immune response to injury. Analysis now defines immune cell origin, disease stage-specific responses, and the effects of age and sex after ischemic stroke.
Cancer cells often rely on glycolysis for energy metabolism. Increased glycolysis leads to the increased production of lactate and H+ ions, which should hypothetically lower intracellular pH. However, we find that tumor cells combat intracellular over-acidification by synthesizing carnosine, especially under hypoxic conditions, which allows them to control lysosome-dependent galectin-9 expression and evade T cell-mediated immune surveillance.
Apart from lifestyle, environment and chance events, genetic factors have a key role in delineating the health and longevity of an individual. Research by Park et al. has now shed light on the role of mammalian GIMAP5, a longevity-assurance (LASS) gene encoding a GTP-binding protein that regulates ceramide synthesis and cellular senescence.
The transcription cofactor TLE3 interacts with RUNX3 and TCF1 to repress the transcription and chromatin accessibility of CD8+ TCM cell signature genes, while simultaneously acting as a coactivator for TBET to facilitate the expression of CD8+ TEM cell signature genes. As such, TLE3 serves as a gatekeeper of CD8+ TCM cell formation.
In this proof-of-concept study, we present a next-generation poxvirus vaccine that features a ‘two-in-one’ immunogen. Our protein vaccine construct, DAM, combines the monkeypox virus antigens A35 and M1, and was produced on the basis of structure-guided design. The DAM subunit vaccine elicited superior antiviral immunity with safety compared to cocktail vaccines or a live vaccinia virus vaccine.
In this Review, Wilfahrt and Delgoffe discuss how T cells integrate nutrient sensing with activating stimuli to shape their differentiation and sensitivity to metabolites.
Sepsis is a global health issue in great need of effective therapies. Analysis of gene expression profiles in different tissues and at the whole-body level in mice enabled the characterization of the organism-wide host response to sepsis, which will help to build a unified mechanistic framework for the disease.