Reviews & Analysis

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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.

    • Kathrin M. Bernt
    News & Views
  • 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.

    • Calvin Jon A. Leonen
    • Hironori Funabiki
    News & Views
  • 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.

    • Thi H. O. Nguyen
    • Katherine Kedzierska
    News & Views
  • 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.

    • J. Magarian Blander
    • Yuhua Shi
    News & Views
  • 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.

    • Anne-Gaëlle Goubet
    • Mikaël J. Pittet
    News & Views
  • Visceral adipose tissue hosts at least two populations of mature FOXP3+ regulatory T cells, which together can preserve systemic metabolism and control inflammation.

    • Melanie Grusdat
    • Dirk Brenner
    News & Views
  • 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.

    • Xuezheng Wang
    • Keji Zhao
    News & Views
  • 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.

    • Charles-Antoine Dutertre
    News & Views
  • 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.

    • Danye Jiang
    • Louise McCullough
    News & Views
  • 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.

    • Atrayee Gope
    • Claudio Mauro
    News & Views
  • 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.

    • Jian Shen
    • Siying Lin
    • Weiguo Cui
    News & Views
  • 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.

    • Wataru Ise
    • Tomohiro Kurosaki
    News & Views
  • 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.

    • Oliver Pabst
    • Vuk Cerovic
    News & Views
  • 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.

    • Shifaa M. Abdin
    • Daniela Paasch
    • Nico Lachmann
    News & Views
  • 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.

    • Monica Casucci
    • Chiara Bonini
    • Eliana Ruggiero
    News & Views
  • BCG vaccination provides protection against unrelated viral infections. The vaccine induces protective integrated organ immunity through biphasic activation of innate and adaptive immune cells.

    • Maria Rescigno
    News & Views
  • 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.

    • Camila D. Odio
    • Rosemary A. Aogo
    • Leah C. Katzelnick
    News & Views