Reviews & Analysis

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 (T_reg) cells can suppress antitumor immunity. Unlike in splenic T_reg 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⁺ T_CM cell signature genes, while simultaneously acting as a coactivator for TBET to facilitate the expression of CD8⁺ T_EM cell signature genes. As such, TLE3 serves as a gatekeeper of CD8⁺ T_CM 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.

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 effectiveness of pneumococcal vaccines declines with age for unknown reasons. We studied the responses of older adults to the 23-valent PPSV23 and the 13-valent PCV13, identifying distinct baseline immune characteristics associated with vaccine responsiveness, including a cytotoxicity signature associated with weaker responses to PCV13.

The alarmin IL-33 activates type 1 and type 2 immune cells via its receptor ST2 in a context-specific manner. We discovered a type 1 immunity-restricted promoter of the ST2-coding gene Il1rl1, which is located far upstream of the curated gene and is crucial for antiviral CD8⁺ cytotoxic T cell and CD4⁺ T_H1 cell responses.

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.