Volume 25 Issue 2, February 2024

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.

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.

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 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.

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.

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.

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.

In this Review, Wilfahrt and Delgoffe discuss how T cells integrate nutrient sensing with activating stimuli to shape their differentiation and sensitivity to metabolites.

Roan et al. use Olink and single‐cell RNA sequencing (scRNA-seq) to show a dysregulated crosstalk between the cellular and humoral immune responses in individuals with long COVID 8 months postinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Chevrier and colleagues uncovered a hierarchical cytokine circuit arising from the pairwise effects of TNF with IL-18, IFN-γ or IL-1β, which explains the organism-wide response of the host to bacterial sepsis.

Ikaros, Helios and Aiolos are transcription factors involved in lymphocyte development. Here the authors dissect the regulatory role of these Ikaros family members to understand their contribution to NK cell development and functions.

Löhning and colleagues identify an alternative promoter for the Il1rl1 gene that drives IL-33 receptor expression in cytotoxic T cells and T-helper 1 cells

Here the authors show that immune cell exclusion and immunosuppression in the melanoma microenviromment are driven by nerve growth factor interactions with tropomyosin receptor kinase A on melanoma cells and that a tropomyosin receptor kinase inhibitor can sensitize these tumors to immune checkpoint blockade.

Lenardo and colleagues identify a new human genetic disease, GISELL, whereby ceramide lipid homeostasis is disrupted, thereby altering T cell longevity. Deficiency of GTPase of the immunity-associated protein 5 (GIMAP5) in patients leads to cellular senescence, immunodeficiency and early mortality.

Xue and colleagues show that the transcription cofactor Tle3 cooperates with Runx3, Tcf1 and Tbet to limit a central memory and promote an effector memory cell signature in CD8⁺ T cells.

Gao and colleagues report a structure-guided chimeric antigen based on the A35 and M1 antigens of the mpox virus (MPXV) that induces strong MPXV-specific antibody responses and protection against lethal doses of vaccinia virus in mice.

Ravichandran et al. performed a systems immunology study to profile the responses to pneumococcal vaccines in older adults. They identified distinct baseline features that could capture responses to Prevnar and Pneumovax and sex-biased differences in Prevnar responses.

Terminally differentiated plasma cells reside in multiple tissues to contribute to local immunity. Nutt and colleagues examined tissue-specific differences in long-lived plasma cell lifespan and function, identifying unique transcriptional attributes in addition to the core plasma cell program.

Sagar and colleagues provide a comprehensive single-cell multimodal landscape of γδ T cells in various mouse tissues, unveiling site-specific adaptations and highlighting key tissue residency features of γδ T cells.

Anrather and colleagues provide a longitudinal single-cell transcriptomic atlas of brain and mouse blood following stroke, describing brain-infiltrating leukocytes, circulating leukocytes, microglia and endothelium diversity over the ischemic–reperfusion time