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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.
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.
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.
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.
Anatomical separation exists between the generation and lodging sites of plasma cells. Transcriptome analysis of tissue-resident plasma cells provides important insights into how newly generated plasma cells acquire longevity.
The use of T cell receptor signatures to track activated spike-specific T cell dynamics between recovery from SARS-CoV-2 infection and subsequent mRNA vaccination shows that vaccination effectively recruits pre-existing memory and new CD8+ T cell clonotypes.
Epithelial cells, macrophages and T cells are linked in a previously unknown regulatory circuit. Sensing of interferon-γ triggers antigen presentation by colonic epithelial cells, enabling T cells to lower extracellular ATP levels and reduce inflammation.
Expressing chimeric antigen receptors (CARs) in macrophages has led to promising results in preclinical and clinical work. Now, induced pluripotent stem cells have been combined with a second-generation CAR to achieve macrophage rewiring and to broaden the applicability of the approach to solid malignancies.
T cells exist in many functional states, and dynamic transitions from one state to another affect the outcome of adoptive T cell therapy. FOXP1 and KLF2 are now identified as transcriptional regulators of the stemness of CD8+ CAR-T cells and the bifurcation of stem-like CD8+ CAR-T cells into effector and exhausted subsets, respectively.
BCG vaccination provides protection against unrelated viral infections. The vaccine induces protective integrated organ immunity through biphasic activation of innate and adaptive immune cells.
The immune response to dengue virus infection is a well-coordinated balancing act. New research shows that an imbalanced response — driven partially by the productive infection of antigen-presenting cells — is associated with progression to severe disease.